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1. Banerji U, Affolter A, Judson I, Marais R, Workman P: BRAF and NRAS mutations in melanoma: potential relationships to clinical response to HSP90 inhibitors. Mol Cancer Ther; 2008 Apr;7(4):737-9
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  • [Title] BRAF and NRAS mutations in melanoma: potential relationships to clinical response to HSP90 inhibitors.
  • Oncogenic BRAF and NRAS mutations are frequent in malignant melanoma.
  • Here, we explore the possible relationship between tumor BRAF and NRAS mutations and clinical response to 17-AAG in six patients with metastatic malignant melanoma who received pharmacologically active doses of 17-AAG as part of a phase I clinical trial.
  • These preliminary results suggest that BRAF and NRAS mutation status should be determined in prospective phase II studies of HSP90 inhibitors in melanoma.

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  • (PMID = 18375819.001).
  • [ISSN] 1535-7163
  • [Journal-full-title] Molecular cancer therapeutics
  • [ISO-abbreviation] Mol. Cancer Ther.
  • [Language] ENG
  • [Grant] United Kingdom / Cancer Research UK / / 10433; United Kingdom / Cancer Research UK / / 10437; United Kingdom / Cancer Research UK / /
  • [Publication-type] Clinical Trial, Phase I; Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Benzoquinones; 0 / HSP90 Heat-Shock Proteins; 0 / Lactams, Macrocyclic; 4GY0AVT3L4 / tanespimycin; EC 2.7.11.1 / BRAF protein, human; EC 2.7.11.1 / Proto-Oncogene Proteins B-raf
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2. Cassaday RD, Sondel PM, King DM, Macklin MD, Gan J, Warner TF, Zuleger CL, Bridges AJ, Schalch HG, Kim KM, Hank JA, Mahvi DM, Albertini MR: A phase I study of immunization using particle-mediated epidermal delivery of genes for gp100 and GM-CSF into uninvolved skin of melanoma patients. Clin Cancer Res; 2007 Jan 15;13(2 Pt 1):540-9
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  • [Title] A phase I study of immunization using particle-mediated epidermal delivery of genes for gp100 and GM-CSF into uninvolved skin of melanoma patients.
  • PURPOSE: We examined in vivo particle-mediated epidermal delivery (PMED) of cDNAs for gp100 and granulocyte macrophage colony-stimulating factor (GM-CSF) into uninvolved skin of melanoma patients.
  • The aims of this phase I study were to assess the safety and immunologic effects of PMED of these genes in melanoma patients.
  • EXPERIMENTAL DESIGN: Two treatment groups of six patients each were evaluated.
  • Group I received PMED with cDNA for gp100, and group II received PMED with cDNA for GM-CSF followed by PMED for gp100 at the same site.
  • One vaccine site per treatment cycle was biopsied and divided for protein extraction and sectioning to assess transgene expression, gold-bead penetration, and dendritic cell infiltration.
  • Exploratory immunologic monitoring of HLA-A2(+) patients included flow cytometric analyses of peripheral blood lymphocytes and evaluation of delayed-type hypersensitivity to gp100 peptide.
  • GM-CSF transgene expression in vaccinated skin sites was detected.
  • CONCLUSIONS: PMED with cDNAs for gp100 alone or in combination with GM-CSF is well tolerated by patients with melanoma.
  • This technique yields biologically active transgene expression in normal human skin.
  • [MeSH-major] Administration, Cutaneous. Granulocyte-Macrophage Colony-Stimulating Factor / administration & dosage. Melanoma / drug therapy. Membrane Glycoproteins / administration & dosage. Skin / drug effects. Skin / metabolism. Skin Neoplasms / drug therapy
  • [MeSH-minor] Adult. Aged. Autoimmunity. Biopsy. DNA, Complementary / metabolism. Female. Humans. Male. Middle Aged. Vaccines, DNA. gp100 Melanoma Antigen

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  • (PMID = 17255276.001).
  • [ISSN] 1078-0432
  • [Journal-full-title] Clinical cancer research : an official journal of the American Association for Cancer Research
  • [ISO-abbreviation] Clin. Cancer Res.
  • [Language] eng
  • [Grant] United States / NCRR NIH HHS / RR / M01 RR 003186; United States / NCI NIH HHS / CA / P30 CA 14520; United States / NCI NIH HHS / CA / R29 CA 6846; United States / NCI NIH HHS / CA / U01 CA 61498
  • [Publication-type] Clinical Trial, Phase I; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / DNA, Complementary; 0 / Membrane Glycoproteins; 0 / PMEL protein, human; 0 / Vaccines, DNA; 0 / gp100 Melanoma Antigen; 83869-56-1 / Granulocyte-Macrophage Colony-Stimulating Factor
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3. Janik JE, Miller LL, Korn EL, Stevens D, Curti BD, Smith JW 2nd, Sznol M, Conlon KC, Sharfman W, Urba WJ, Gause BL, Longo DL: A prospective randomized phase II trial of GM-CSF priming to prevent topotecan-induced neutropenia in chemotherapy-naive patients with malignant melanoma or renal cell carcinoma. Blood; 2001 Apr 1;97(7):1942-6
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  • [Title] A prospective randomized phase II trial of GM-CSF priming to prevent topotecan-induced neutropenia in chemotherapy-naive patients with malignant melanoma or renal cell carcinoma.
  • We conducted a phase II randomized trial of recombinant granculocyte-macrophage colony-stimulating factor (GM-CSF) administered before topotecan chemotherapy to determine whether it could prevent myelosuppression and to determine the antitumor activity of this topoisomerase I inhibitor in 53 patients with metastatic malignant melanoma and renal cell cancer.
  • Patients randomly assigned to receive GM-CSF priming were treated with GM-CSF at 250 microg/m(2) twice daily for 5 days before treatment.
  • The primary analysis was restricted to the protective effects seen during the first cycle of therapy.
  • The protective effects of GM-CSF extended to the second cycle of treatment.
  • Chemotherapy-induced anemia and thrombocytopenia were similar in both groups.
  • One partial response was seen in a patient with melanoma, and one patient with renal cell cancer had complete regression of pulmonary metastases and was rendered disease-free by nephrectomy. (Blood.
  • [MeSH-major] Antineoplastic Agents / adverse effects. Carcinoma, Renal Cell / drug therapy. Granulocyte-Macrophage Colony-Stimulating Factor / therapeutic use. Kidney Neoplasms / drug therapy. Melanoma / drug therapy. Neutropenia / prevention & control. Skin Neoplasms / drug therapy. Topotecan / adverse effects
  • [MeSH-minor] Anemia / chemically induced. Diabetes Mellitus, Type 1 / complications. Humans. Hypotension / chemically induced. Premedication. Prospective Studies. Remission Induction. Severity of Illness Index. Stroke / etiology. Thrombocytopenia / chemically induced. Treatment Outcome

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  • (PMID = 11264156.001).
  • [ISSN] 0006-4971
  • [Journal-full-title] Blood
  • [ISO-abbreviation] Blood
  • [Language] eng
  • [Publication-type] Clinical Trial; Clinical Trial, Phase II; Journal Article; Randomized Controlled Trial
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 7M7YKX2N15 / Topotecan; 83869-56-1 / Granulocyte-Macrophage Colony-Stimulating Factor
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4. Fonsatti E, Nicolay HJ, Sigalotti L, Calabrò L, Pezzani L, Colizzi F, Altomonte M, Guidoboni M, Marincola FM, Maio M: Functional up-regulation of human leukocyte antigen class I antigens expression by 5-aza-2'-deoxycytidine in cutaneous melanoma: immunotherapeutic implications. Clin Cancer Res; 2007 Jun 1;13(11):3333-8
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  • [Title] Functional up-regulation of human leukocyte antigen class I antigens expression by 5-aza-2'-deoxycytidine in cutaneous melanoma: immunotherapeutic implications.
  • EXPERIMENTAL DESIGN: The effect of 5-aza-CdR on the constitutive expression of gp100 was investigated in 11 human melanoma cell lines by real-time reverse transcription-PCR and indirect immunofluorescence (IIF) analyses.
  • 5-aza-CdR-mediated changes in the levels of expression of human leukocyte antigen (HLA) class I antigens and HLA-A2 allospecificity, intercellular adhesion molecule-1 (ICAM-1), and leukocyte-function-associated antigen-3 were investigated by IIF analysis on melanoma cells under study.
  • The recognition of gp100-positive Mel 275 melanoma cells, treated or not with 5-aza-CdR, by HLA-A2-restricted gp100((209-217))-specific CTL was investigated by (51)Cr-release assays, IFN-gamma release and IFN-gamma ELISPOT assays.
  • RESULTS: The constitutive expression of gp100 was not affected by 5-aza-CdR on all melanoma cells investigated.
  • Compared with untreated cells, the exposure of Mel 275 melanoma cells to 5-aza-CdR significantly (P < 0.05) up-regulated their expression of HLA class I antigens and of ICAM-1.
  • These phenotypic changes significantly (P < 0.05) increased the lysis of 5-aza-CdR-treated Mel 275 melanoma cells by gp100-specific CTL and increased their IFN-gamma release.
  • 5-aza-CdR treatment of Mel 275 cells also induced a higher number of gp100-specific CTL to secrete IFN-gamma.
  • CONCLUSIONS: Treatment with 5-aza-CdR improves the recognition of melanoma cells by gp100-specific CTL through the up-regulation of HLA class I antigens expression; ICAM-1 also contributes to this phenomenon.
  • These findings highlight a broader range of therapeutic implications of 5-aza-CdR when used in association with active or adoptive immunotherapeutic approaches against a variety of melanoma-associated antigens.
  • [MeSH-major] Azacitidine / analogs & derivatives. Gene Expression Regulation, Neoplastic. Histocompatibility Antigens Class I / biosynthesis. Immunotherapy / methods. Melanoma / drug therapy. Melanoma / immunology. Skin Neoplasms / drug therapy. Skin Neoplasms / immunology. T-Lymphocytes, Cytotoxic / immunology
  • [MeSH-minor] Cell Line, Tumor. Fluorescent Antibody Technique, Indirect. Humans. Interferon-gamma / metabolism. Membrane Glycoproteins / metabolism. Reverse Transcriptase Polymerase Chain Reaction. Up-Regulation. gp100 Melanoma Antigen

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  • (PMID = 17545540.001).
  • [ISSN] 1078-0432
  • [Journal-full-title] Clinical cancer research : an official journal of the American Association for Cancer Research
  • [ISO-abbreviation] Clin. Cancer Res.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Histocompatibility Antigens Class I; 0 / Membrane Glycoproteins; 0 / PMEL protein, human; 0 / gp100 Melanoma Antigen; 776B62CQ27 / decitabine; 82115-62-6 / Interferon-gamma; M801H13NRU / Azacitidine
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5. Baloglu A, Bezircioglu I, Cetinkaya B, Yavuzcan A: Primary malignant melanoma of the vagina. Arch Gynecol Obstet; 2009 Nov;280(5):819-22
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  • [Title] Primary malignant melanoma of the vagina.
  • BACKGROUND: Primary vaginal melanoma is a rare, highly malignant, and poor prognostic disease.
  • CASE: The 51-year-old patient with diagnosis of vaginal malignant melanoma was referred to our clinic.
  • Since detection of pervasive brown lesions in the vagina total vaginectomy was performed.
  • At pathological investigation melanoma was not determined.
  • Cisplatin and tremozolamide chemotherapy was administered for six cycles after surgery.
  • The patient is alive and disease-free at 18th month of the diagnosis of the disease.
  • CONCLUSION: The impact of therapy on outcome of primary vaginal malign melanomas is poorly understood.
  • We presented a case of FIGO stage I primary vaginal malignant melanoma, which metastasized to the paraaortic lymph nodes 9 months after the primary operation.
  • [MeSH-major] Melanoma / pathology. Melanoma / therapy. Vaginal Neoplasms / pathology. Vaginal Neoplasms / therapy
  • [MeSH-minor] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Cisplatin / administration & dosage. Dacarbazine / administration & dosage. Dacarbazine / analogs & derivatives. Female. Humans. Interferon-alpha / administration & dosage. Lymphatic Metastasis. Middle Aged

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  • (PMID = 19242707.001).
  • [ISSN] 1432-0711
  • [Journal-full-title] Archives of gynecology and obstetrics
  • [ISO-abbreviation] Arch. Gynecol. Obstet.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / Interferon-alpha; 7GR28W0FJI / Dacarbazine; 85622-93-1 / temozolomide; Q20Q21Q62J / Cisplatin
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6. Ribas A, Kirkwood JM, Atkins MB, Whiteside TL, Gooding W, Kovar A, Gillies SD, Kashala O, Morse MA: Phase I/II open-label study of the biologic effects of the interleukin-2 immunocytokine EMD 273063 (hu14.18-IL2) in patients with metastatic malignant melanoma. J Transl Med; 2009;7:68
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  • [Title] Phase I/II open-label study of the biologic effects of the interleukin-2 immunocytokine EMD 273063 (hu14.18-IL2) in patients with metastatic malignant melanoma.
  • BACKGROUND: To explore the biological activity of EMD 273063 (hu14.18-IL2), a humanized anti-GD2 monoclonal antibody fused to interleukin-2 (IL2), in patients with unresectable, stage IV cutaneous melanoma as measured by induction of immune activation at the tumor site and in peripheral blood.
  • Peripheral blood was analyzed for T cell and natural killer cell phenotype and frequency, as well as levels of soluble IL2 receptor (sIL2R), IL10, IL6, tumor necrosis factor alpha and neopterin.
  • Biopsies of tumor metastasis were performed prior to therapy and at day 10 of the first 2 cycles to study lymphocyte accumulation by immunohistochemistry.
  • RESULTS: Treatment was generally well tolerated and there were no study drug-related grade 4 adverse events.
  • Best response on therapy was stable disease in 2 patients.
  • There were no objective tumor regressions by standard response criteria.
  • There was evidence of increased tumor infiltration by T cells, but not NK cells, in most post-dosing biopsies, suggesting recruitment of immune cells to the tumor site.
  • [MeSH-major] Antibodies, Monoclonal / therapeutic use. Cytokines / therapeutic use. Interleukin-2 / therapeutic use. Melanoma / pathology. Melanoma / therapy. Skin Neoplasms / pathology. Skin Neoplasms / therapy
  • [MeSH-minor] Adult. Aged. Area Under Curve. Biopsy. Female. Follow-Up Studies. Half-Life. Humans. Immunohistochemistry. Male. Metabolic Clearance Rate. Middle Aged. Neoplasm Metastasis. Neoplasm Staging. Time Factors. Treatment Outcome

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  • (PMID = 19640287.001).
  • [ISSN] 1479-5876
  • [Journal-full-title] Journal of translational medicine
  • [ISO-abbreviation] J Transl Med
  • [Language] eng
  • [Publication-type] Clinical Trial, Phase I; Clinical Trial, Phase II; Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Cytokines; 0 / EMD 273063 antibody, human; 0 / Interleukin-2
  • [Other-IDs] NLM/ PMC2724499
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7. Escudier B, Lassau N, Angevin E, Soria JC, Chami L, Lamuraglia M, Zafarana E, Landreau V, Schwartz B, Brendel E, Armand JP, Robert C: Phase I trial of sorafenib in combination with IFN alpha-2a in patients with unresectable and/or metastatic renal cell carcinoma or malignant melanoma. Clin Cancer Res; 2007 Mar 15;13(6):1801-9
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  • [Title] Phase I trial of sorafenib in combination with IFN alpha-2a in patients with unresectable and/or metastatic renal cell carcinoma or malignant melanoma.
  • PURPOSE: To determine the safety, maximum tolerated dose, pharmacokinetics, and efficacy, and to evaluate biomarkers, of the multikinase inhibitor sorafenib plus IFN alpha-2a in advanced renal cell carcinoma (RCC) or melanoma.
  • Tumor response was assessed by Response Evaluation Criteria in Solid Tumors and dynamic contrast-enhanced ultrasonography.
  • RESULTS: Thirteen patients received at least one dose of sorafenib plus IFN (12 RCC; one melanoma).
  • Most frequently reported drug-related adverse events were grade 2 or less in severity, including fatigue, diarrhea, nausea, alopecia, and hand-foot skin reaction.
  • One (7.7%) RCC patient achieved partial response and eight (61.5%) had stable disease (including the melanoma patient).
  • There were no significant changes in absolute values of lymphocytes, levels of proangiogenic cytokines, or inhibition of phosphorylated extracellular signal-regulated kinase in T cells or natural killer cells, with combination therapy.
  • CONCLUSIONS: This sorafenib combination was well tolerated, with preliminary antitumor activity in advanced RCC and melanoma patients.
  • There were no drug-drug interactions and the recommended dose for future studies is sorafenib 400 mg twice daily plus IFN 9 MIU.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Benzenesulfonates / administration & dosage. Carcinoma, Renal Cell / drug therapy. Interferon-alpha / administration & dosage. Kidney Neoplasms / drug therapy. Melanoma / drug therapy. Pyridines / administration & dosage
  • [MeSH-minor] Adult. Aged. Algorithms. Biomarkers, Tumor / analysis. Female. Humans. Immune System / drug effects. Male. Middle Aged. Niacinamide / analogs & derivatives. Phenylurea Compounds. Recombinant Proteins. Treatment Outcome

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  • (PMID = 17363536.001).
  • [ISSN] 1078-0432
  • [Journal-full-title] Clinical cancer research : an official journal of the American Association for Cancer Research
  • [ISO-abbreviation] Clin. Cancer Res.
  • [Language] eng
  • [Publication-type] Clinical Trial, Phase I; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Benzenesulfonates; 0 / Biomarkers, Tumor; 0 / Interferon-alpha; 0 / Phenylurea Compounds; 0 / Pyridines; 0 / Recombinant Proteins; 25X51I8RD4 / Niacinamide; 76543-88-9 / interferon alfa-2a; 9ZOQ3TZI87 / sorafenib
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8. Azzabi A, Hughes AN, Calvert PM, Plummer ER, Todd R, Griffin MJ, Lind MJ, Maraveyas A, Kelly C, Fishwick K, Calvert AH, Boddy AV: Phase I study of temozolomide plus paclitaxel in patients with advanced malignant melanoma and associated in vitro investigations. Br J Cancer; 2005 Mar 28;92(6):1006-12
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  • [Title] Phase I study of temozolomide plus paclitaxel in patients with advanced malignant melanoma and associated in vitro investigations.
  • Melanoma cell lines A375P and DX3 were treated with temozolomide and either paclitaxel or epothilone B.
  • In a clinical study, 21 patients with malignant melanoma were treated with increasing doses of temozolomide (orally, days 1-5), in combination with a fixed dose of paclitaxel (i.v. infusion day 1), followed by dose escalation of the latter drug.
  • Cycles of treatment were repeated every 3 weeks.
  • All three compounds were active against the melanoma cell lines, with epothilone B being the most potent.
  • Dose escalation of both drugs to clinically active doses was possible, with no dose-limiting toxicities observed at 200 mg m(-2) day(-1) temozolomide and 225 mg m(-2) day(-1) paclitaxel.
  • One patient remains alive and symptom-free at 4 years after treatment.
  • Further evaluation of these combinations in melanoma is warranted.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Dacarbazine / analogs & derivatives. Melanoma / drug therapy
  • [MeSH-minor] Adult. Aged. Cell Line, Tumor. Female. Humans. Male. Middle Aged. Paclitaxel / administration & dosage. Paclitaxel / pharmacokinetics

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  • (PMID = 15756276.001).
  • [ISSN] 0007-0920
  • [Journal-full-title] British journal of cancer
  • [ISO-abbreviation] Br. J. Cancer
  • [Language] eng
  • [Publication-type] Clinical Trial; Clinical Trial, Phase I; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 7GR28W0FJI / Dacarbazine; 85622-93-1 / temozolomide; P88XT4IS4D / Paclitaxel
  • [Other-IDs] NLM/ PMC2361941
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9. Freudlsperger C, Dahl A, Hoffmann J, Reinert S, Schumacher U: Mistletoe lectin-I augments antiproliferative effects of the PPARgamma agonist rosiglitazone on human malignant melanoma cells. Phytother Res; 2010 Sep;24(9):1354-8
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  • [Title] Mistletoe lectin-I augments antiproliferative effects of the PPARgamma agonist rosiglitazone on human malignant melanoma cells.
  • As malignant melanoma cells are highly resistant to conventional chemotherapy, survival rates after tumor spread remain poor and hence there is an urgent need for new therapeutic options.
  • For both mistletoe lectin-I (ML-I) and the thiazolidinediones as synthetic ligands of the peroxisome proliferator-activated receptor gamma (PPARgamma) an antiproliferative effect on malignant melanoma cells has previously been shown.
  • Hence, the aim of this study was to investigate whether the combination of ML-I and the PPARgamma ligand rosiglitazone is more efficacious in the treatment of malignant melanoma cells than either agent alone.
  • Proliferation of three human melanoma cell lines treated with ML-I, rosiglitazone and the combination of both was measured in a broad concentration range (0.0001-100 microg/mL) using the XTT cell proliferation assay.
  • Combined application tremendously increased the antiproliferative effect on all three melanoma cell lines compared with single agent treatment.
  • In conclusion, this study shows that the combination of ML-I with rosiglitazone significantly augments their antiproliferative effect on malignant melanoma cells in comparison with their single agent application, which might be a promising tool for further therapeutic studies.
  • [MeSH-major] Antineoplastic Agents, Phytogenic / therapeutic use. Melanoma / drug therapy. PPAR gamma / agonists. Phytotherapy. Ribosome Inactivating Proteins, Type 2 / therapeutic use. Thiazolidinediones / therapeutic use. Toxins, Biological / therapeutic use. Viscum album / chemistry
  • [MeSH-minor] Cell Line, Tumor. Cell Proliferation / drug effects. Chemotherapy, Adjuvant. Drug Synergism. Drug Therapy, Combination. Humans. Plant Extracts / pharmacology. Plant Extracts / therapeutic use

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  • [Copyright] Copyright 2010 John Wiley & Sons, Ltd.
  • (PMID = 20812278.001).
  • [ISSN] 1099-1573
  • [Journal-full-title] Phytotherapy research : PTR
  • [ISO-abbreviation] Phytother Res
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antineoplastic Agents, Phytogenic; 0 / PPAR gamma; 0 / Plant Extracts; 0 / Ribosome Inactivating Proteins, Type 2; 0 / Thiazolidinediones; 0 / Toxins, Biological; 0 / mistletoe lectin I; 05V02F2KDG / rosiglitazone
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10. Thies A, Pfüller U, Schachner M, Horny HP, Molls I, Schumacher U: Binding of mistletoe lectins to cutaneous malignant melanoma: implications for prognosis and therapy. Anticancer Res; 2001 Jul-Aug;21(4B):2883-7
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  • [Title] Binding of mistletoe lectins to cutaneous malignant melanoma: implications for prognosis and therapy.
  • However, no data concerning the three mistletoe lectins (MLs) and the spread of malignant melanoma have been published.
  • MATERIALS AND METHODS: The binding status of ML-I, -II and -III was histochemically assessed in 100 malignant melanomas and correlated with metastasis in a 10 year follow-up period.
  • CONCLUSION: Since ML-I is specific for galactose, high density galactose expression in malignant melanoma is a predictor of poor prognosis.
  • [MeSH-major] Antineoplastic Agents, Phytogenic / metabolism. Lectins / metabolism. Melanoma / metabolism. Plant Preparations. Plant Proteins. Skin Neoplasms / metabolism. Toxins, Biological / metabolism
  • [MeSH-minor] Adjuvants, Immunologic / pharmacology. Adult. Aged. Aged, 80 and over. Disease-Free Survival. Female. Follow-Up Studies. Humans. Killer Cells, Natural / drug effects. Killer Cells, Natural / pathology. Life Tables. Male. Middle Aged. Neoplasm Metastasis. Prognosis. Ribosome Inactivating Proteins, Type 2

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  • (PMID = 11712781.001).
  • [ISSN] 0250-7005
  • [Journal-full-title] Anticancer research
  • [ISO-abbreviation] Anticancer Res.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Greece
  • [Chemical-registry-number] 0 / Adjuvants, Immunologic; 0 / Antineoplastic Agents, Phytogenic; 0 / Lectins; 0 / Plant Preparations; 0 / Plant Proteins; 0 / Ribosome Inactivating Proteins, Type 2; 0 / Toxins, Biological; 0 / mistletoe lectin I; 0 / ribosome inactivating protein, Viscum
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11. Dreno B: [Interferons and malignant melanoma]. Rev Med Interne; 2002 Nov;23 Suppl 4:489s-493s
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  • [Title] [Interferons and malignant melanoma].
  • [Transliterated title] Interféron et mélanome malin.
  • BACKGROUND: Alpha interferon is currently used in the treatment of malignant melanoma mainly as adjuvant therapy at the first stage of the illness (primary tumor) and at the second stage (lymph node invasion).
  • CURRENT POSITION AND MAIN POINTS: At metastatic stage, interferon alpha has no adverse indication when used alone.
  • However, studies are on going to assess its potential synergistic effect combined with chemotherapy and its interest for maintaining clinical response.
  • Beta and gamma interferon have no adverse indication in the treaTment of malignant melanoma.
  • PERSPECTIVE: Although its action has been mainly demonstrated on relapse free survival, and the impact on quality of life remains important, additional new studies will be required to confirm its interest as adjuvant therapy for melanoma.
  • In addition, the future use of pegylated interferon which would permit a reduction in the number of injections is of a significant interest.

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  • (PMID = 12481404.001).
  • [ISSN] 0248-8663
  • [Journal-full-title] La Revue de medecine interne
  • [ISO-abbreviation] Rev Med Interne
  • [Language] FRE
  • [Publication-type] English Abstract; Journal Article; Review
  • [Publication-country] France
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Interferon-alpha
  • [Number-of-references] 19
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12. Romanini A, Manca G, Pellegrino D, Murr R, Sarti S, Bianchi F, Alsharif A, Orlandini C, Zucchi V, Castagna M, Gandini D, Salimbeni G, Ghiara F, Barachini P, Mariani G: Molecular staging of the sentinel lymph node in melanoma patients: correlation with clinical outcome. Ann Oncol; 2005 Nov;16(11):1832-40
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  • [Title] Molecular staging of the sentinel lymph node in melanoma patients: correlation with clinical outcome.
  • BACKGROUND: This study was designed to determine the debated prognostic significance of reverse transcriptase-polymerase chain reaction (RT-PCR) positivity in melanoma patients' sentinel lymph node (SLN) negative by conventional histopathology (PATH).
  • PATIENTS AND METHODS: Patients with primary stage I-II cutaneous melanoma underwent radioguided sentinel lymphadenectomy.
  • Their SLNs were assessed for tyrosinase (Tyr) and melanoma antigens recognized by T-cells (MART-1) mRNA expression using RT-PCR, in parallel with hematoxylin and eosin staining and immunohistochemistry.
  • Tyr and MART-1 expression in the SLNs were correlated with PATH assay results, standard prognostic factors, time to progression and overall survival.
  • CONCLUSIONS: RT-PCR is more sensitive than PATH to detect SLN metastases and it is a reliable predictor of disease relapse in stage I-II melanoma patients.

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  • (PMID = 16107497.001).
  • [ISSN] 0923-7534
  • [Journal-full-title] Annals of oncology : official journal of the European Society for Medical Oncology
  • [ISO-abbreviation] Ann. Oncol.
  • [Language] ENG
  • [Publication-type] Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antigens, Neoplasm; 0 / MART-1 Antigen; 0 / MLANA protein, human; 0 / Neoplasm Proteins; 0 / RNA, Messenger; EC 1.14.18.1 / Monophenol Monooxygenase
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13. Pellegrino D, Bellina CR, Manca G, Boni G, Grosso M, Volterrani D, Desideri I, Bianchi F, Bottoni A, Ciliberti V, Salimbeni G, Gandini D, Castagna M, Zucchi V, Romanini A, Bianchi R: Detection of melanoma cells in peripheral blood and sentinel lymph nodes by RT-PCR analysis: a comparative study with immunohistochemistry. Tumori; 2000 Jul-Aug;86(4):336-8
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  • [Title] Detection of melanoma cells in peripheral blood and sentinel lymph nodes by RT-PCR analysis: a comparative study with immunohistochemistry.
  • The presence of lymph node metastases is the best prognostic factor for predicting relapse or survival in melanoma patients.
  • It has been demonstrated that melanoma metastases spread through the first lymph node(s) draining the tumor (sentinel lymph node, SN) to the lymphatic system and that detection of melanoma cells in peripheral blood directly correlates with prognosis in melanoma.
  • To identify lymph node metastases and circulating melanocytes, we developed a single-step reverse transcriptase-polymerase chain reaction assay (RT-PCR) for detection of two melanoma-specific markers: the tyrosinase gene, which encodes an enzyme associated with melanin synthesis, and melanoma antigen-related T-cells, which are present in tumor infiltrating T-lymphocytes.
  • This method detects two tumor cells in a background of 10(7) lymphocytes.
  • Thirty patients with stage I-IV cutaneous melanoma entered the study.
  • Blood samples were taken preoperatively, one month after excision of the primary melanoma lesion and the SN or total lymphadenectomy, and before the start of chemotherapy and every three months thereafter in metastatic patients.
  • The preliminary results indicate that RT-PCR for melanoma markers is a sensitive and valuable method for the detection of micrometastases and for early diagnosis and staging of melanoma.
  • [MeSH-major] Antigens, Neoplasm / genetics. Lymph Nodes / pathology. Melanoma / pathology. Monophenol Monooxygenase / genetics. RNA, Neoplasm / analysis. Reverse Transcriptase Polymerase Chain Reaction. Sentinel Lymph Node Biopsy. Skin Neoplasms / pathology. T-Lymphocytes / pathology

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  • (PMID = 11016721.001).
  • [ISSN] 0300-8916
  • [Journal-full-title] Tumori
  • [ISO-abbreviation] Tumori
  • [Language] eng
  • [Publication-type] Comparative Study; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antigens, Neoplasm; 0 / RNA, Neoplasm; 0 / Radiopharmaceuticals; 0 / Technetium Tc 99m Aggregated Albumin; EC 1.14.18.1 / Monophenol Monooxygenase
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14. Martín-Algarra S, Espinosa E, Rubió J, López López JJ, Manzano JL, Carrión LA, Plazaola A, Tanovic A, Paz-Ares L: Phase II study of weekly Kahalalide F in patients with advanced malignant melanoma. Eur J Cancer; 2009 Mar;45(5):732-5
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  • [Title] Phase II study of weekly Kahalalide F in patients with advanced malignant melanoma.
  • This phase II clinical trial evaluated the antitumour response of Kahalalide F (KF) 650 microg/m(2) given as a 1-h weekly infusion in advanced malignant melanoma patients, both untreated and those who relapsed or progressed after one line of systemic therapy.
  • Of 24 enrolled patients (median age, 55 years; range, 28-89), 14 patients had been previously treated with chemotherapy or biological therapy.
  • No RECIST responses occurred; five chemotherapy-naïve patients with cutaneous melanoma had disease stabilisation for > or = 3 months; median progression-free survival was 1.7 months (95% CI, 1.2-1.9 months); and median overall survival was 10.8 months (95% CI, 5.0-upper limit not reached).
  • The most common laboratory toxicities were non-cumulative increase of transaminases (ALT/AST) and gamma-glutamyltransferase (GGT).
  • KF was a well-tolerated and safe chemotherapy regimen.
  • Despite a favourable safety profile, this trial was closed after the first stage because of the lack of objective response in patients with malignant melanoma.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Depsipeptides / therapeutic use. Melanoma / drug therapy. Skin Neoplasms / drug therapy
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Female. Humans. Male. Middle Aged. Treatment Outcome

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  • (PMID = 19186051.001).
  • [ISSN] 1879-0852
  • [Journal-full-title] European journal of cancer (Oxford, England : 1990)
  • [ISO-abbreviation] Eur. J. Cancer
  • [Language] eng
  • [Publication-type] Clinical Trial, Phase II; Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Depsipeptides; 149204-42-2 / kahalalide F
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15. López M, Escobar A, Alfaro J, Fodor M, Larrondo M, Ferrada C, Salazar-Onfray F: [Advances in cellular immunotherapy for malignant melanoma]. Rev Med Chil; 2004 Sep;132(9):1115-26
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  • [Title] [Advances in cellular immunotherapy for malignant melanoma].
  • [Transliterated title] Avances en inmunoterapia celular contra el melanoma maligno.
  • An alternative strategy for cancer treatment is the manipulation of the immune system, denominated cancer immunotherapy.
  • Recently, we finalized a clinical phase I protocol, for the treatment of malignant melanoma, using DCs loaded with tumor lysates.
  • We also observed an increase of tumor specific T lymphocytes precursors in the blood, associated to hypersensitivity reactions (DTH) in 60% of the treated patients.
  • Additionally, therapies based on Interleukin-2 (IL-2) have been used with relative success in the treatment of some kind of tumors since 1985.
  • [MeSH-major] Cancer Vaccines / therapeutic use. Dendritic Cells / immunology. Immunotherapy. Interleukin-2 / immunology. Melanoma / therapy. Skin Neoplasms / therapy
  • [MeSH-minor] Antigens, Neoplasm / immunology. Enzyme-Linked Immunosorbent Assay / methods. Humans. Hypersensitivity, Delayed. Pulse Therapy, Drug. T-Lymphocytes, Cytotoxic / immunology

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  • (PMID = 15543770.001).
  • [ISSN] 0034-9887
  • [Journal-full-title] Revista médica de Chile
  • [ISO-abbreviation] Rev Med Chil
  • [Language] spa
  • [Publication-type] Clinical Trial; Clinical Trial, Phase I; English Abstract; Journal Article; Research Support, Non-U.S. Gov't; Review
  • [Publication-country] Chile
  • [Chemical-registry-number] 0 / Antigens, Neoplasm; 0 / Cancer Vaccines; 0 / Interleukin-2
  • [Number-of-references] 80
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16. Schlingensiepen KH, Schlingensiepen R, Steinbrecher A, Hau P, Bogdahn U, Fischer-Blass B, Jachimczak P: Targeted tumor therapy with the TGF-beta 2 antisense compound AP 12009. Cytokine Growth Factor Rev; 2006 Feb-Apr;17(1-2):129-39
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  • [Title] Targeted tumor therapy with the TGF-beta 2 antisense compound AP 12009.
  • TGF-beta overexpression is a hallmark of various malignant tumors.
  • This is due to the pivotal role of TGF-beta as it regulates key mechanisms of tumor development, namely immunosuppression, metastasis, angiogenesis, and proliferation.
  • We have developed a new immunotherapeutic approach for the treatment of malignant tumors based on the specific inhibition of TGF-beta2 by the antisense oligodeoxynucleotide AP 12009.
  • Median survival time after recurrence exceeded the up to date literature data for chemotherapy.
  • A phase I/II study in pancreatic carcinoma and malignant melanoma is currently ongoing.
  • Our results implicate targeted TGF-beta2 suppression as a promising therapeutic approach for malignant tumor therapy.
  • [MeSH-major] Drug Delivery Systems / methods. Gene Expression Regulation, Neoplastic / drug effects. Growth Inhibitors / therapeutic use. Oligodeoxyribonucleotides / therapeutic use. Thionucleotides / therapeutic use. Transforming Growth Factor beta2 / antagonists & inhibitors
  • [MeSH-minor] Animals. Cell Line, Tumor. Humans

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  • (PMID = 16377233.001).
  • [ISSN] 1359-6101
  • [Journal-full-title] Cytokine & growth factor reviews
  • [ISO-abbreviation] Cytokine Growth Factor Rev.
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Growth Inhibitors; 0 / Oligodeoxyribonucleotides; 0 / Thionucleotides; 0 / Trabedersen; 0 / Transforming Growth Factor beta2
  • [Number-of-references] 103
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17. Patel S, Bedikian A, Kim K, Papadopoulos N, Hwu P, Vardeleon A, Prieto V, Bar Eli M, Bronstein Y, Bassett R Jr: A phase II study of gefitinib in patients with metastatic melanoma. J Clin Oncol; 2009 May 20;27(15_suppl):9057

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  • [Title] A phase II study of gefitinib in patients with metastatic melanoma.
  • : 9057 Background: Gefitinib is an inhibitor of epidermal growth factor receptor (EGFR), which is frequently expressed on both choroidal and non-choroidal melanoma cells.
  • We evaluated the clinical efficacy of gefitinib in patients (pts) with metastatic melanoma.
  • METHODS: Pts with stage IV or unresectable or recurrent stage III melanoma and Zubrod performance status of 0 to 2 were eligible.
  • For non-choroidal melanoma, pts must have received systemic cytotoxic therapy, but no more than 2 regimens; for choroidal melanoma, pts could be either chemo-naïve or have received up to 2 systemic cytotoxic therapies.
  • The dose of oral gefitinib was 250 mg daily, and tumor response was evaluated every 6 weeks per RECIST.
  • Ten patients with cutaneous disease were also consented for paired biopsies and blood collection for correlative studies at baseline and after 3 weeks of treatment.
  • RESULTS: Fifty-two pts (46 non-choroidal; 6 choroidal primay) were treated and evaluated for toxicity, and 50 pts were evaluable for response.
  • Median age of pts was 62.5 years, with median Zubrod PS Score of 1.
  • The median number of prior systemic treatments was 1.
  • Forty-one pts (79%) had stage M1c disease.
  • There were no drug-related grade 4 or 5 adverse events (AEs), and fatigue was the only grade 3 AEs in >5% of the patients.
  • There were 2 (4%) partial responses, including a pt with metastatic choroidal melanoma, and 13 pts (26%) had disease stabilization.
  • Median time to progression was 6 weeks, and median overall survival was 4.6 months.
  • Among 7 pts with sufficient tissue on paired biopsies, there were no notable trends in the changes of the expression of pERK1/2, pAKT, or pPAK1 with treatment.
  • Additionally, no trends were identified in serum VEGF or IL-8 levels after treatment.
  • CONCLUSIONS: Gefitinib was well tolerated, but had minimal clinical efficacy as a single-agent therapy for metastatic melanoma of cutaneous origin.
  • There were no consistent changes in the expressions of downstream kinase proteins with gefitinib treatment.

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  • (PMID = 27962131.001).
  • [ISSN] 1527-7755
  • [Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • [ISO-abbreviation] J. Clin. Oncol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
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18. Tarhini AA, Christensen S, Frankel P, Margolin K, Ruel C, Shipe-Spotloe J, DeMark M, Kirkwood JM: Phase II study of aflibercept (VEGF trap) in recurrent inoperable stage III or stage IV melanoma of cutaneous or ocular origin. J Clin Oncol; 2009 May 20;27(15_suppl):9028

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  • [Title] Phase II study of aflibercept (VEGF trap) in recurrent inoperable stage III or stage IV melanoma of cutaneous or ocular origin.
  • METHODS: Phase II study of aflibercept in patients with inoperable stage III or IV melanoma who had received no prior chemotherapy or hormonal therapy.
  • A 2-stage design was adopted focusing upon response rate (RECIST) and 4-month PFS rate.
  • First stage accrual of 21 patients was specified, while final accrual of 41 is planned, with adequate response/4 month PFSR.
  • All had AJCC stage IV melanoma (3M1a, 3M1b, 21M1c).
  • Nine patients had primary ocular melanoma, 16 cutaneous and 2 unknown primary site.
  • Grade 3/4 toxicities included cerebral ischemia (1 patient; 4%), confusion (1; 4%), thrombocytopenia (1; 4%), hypertension (7; 26%), hypotension (1; 4%), left ventricular diastolic dysfunction (1; 4%), fatigue (1; 4%), proteinuria (4; 15%), extraocular muscle paresis (1; 4%), renal failure (1; 4%), back pain (1; 4%), headache (1; 4%).
  • Interim analysis was conducted after the first 21 patients (stage 1).
  • Eight (1 M1a, 1M1b, 6M1c; 4 ocular, 3 cutaneous, 1 unknown primary) of the first 21 patients had at least 4 months of PFS (10 out of 27; 2 additional patients with cutaneous melanoma had SD: 1M1a and 1M1c).
  • One patient (23<sup>rd</sup>; cutaneous, M1c) had a confirmed complete remission.
  • Four patients were taken off study prior to response evaluation for toxicity (3) or treatment refusal (1).
  • One patient is currently disease free who was not evaluable for response (previous surgery and radiofrequency ablation of measurable disease site).
  • CONCLUSIONS: Aflibercept can be administered with acceptable toxicity, and exhibits promising antitumor efficacy against advanced melanoma.
  • This study continues second stage accrual with anticipated closure before June 2009.

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  • (PMID = 27962095.001).
  • [ISSN] 1527-7755
  • [Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • [ISO-abbreviation] J. Clin. Oncol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
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19. Goyal A, Evans WD, Mansel RE: Isolated hyperthermic chemotherapy perfusion for limb melanoma is a safe procedure. J Clin Oncol; 2004 Jul 15;22(14_suppl):7538

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  • [Title] Isolated hyperthermic chemotherapy perfusion for limb melanoma is a safe procedure.
  • : 7538 Background: Isolated limb perfusion(ILP) delivers high dose of chemotherapeutic agent to an extremity with multiple in-transit lesions from cutaneous melanoma.
  • METHODS: 53 perfusions were performed using melphalan, 1.5-2mg/kg (13 prophylactic, 40 therapeutic) and 3 using melphalan in combination with other chemotherapeutic agents (all therapeutic).
  • 75% of the patients had MD Anderson stage III disease.
  • Overall 5-year survival rate was 49% for therapeutic perfusion and 100% for prophylactic perfusion.
  • CONCLUSION: Therapeutic ILP is a suitable treatment for in-transit metastases not amenable to surgery and confined to a limb, since amputation provides no advantage in terms of survival.

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  • (PMID = 28014919.001).
  • [ISSN] 1527-7755
  • [Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • [ISO-abbreviation] J. Clin. Oncol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
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20. Schaadt J, Crowley R, Miller D, Kavanah M: Isolated limb perfusion: a literature review. J Extra Corpor Technol; 2002 Jun;34(2):130-43
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  • However, the incidence of melanoma is rising steadily, as are the efforts and resources allocated to its treatment.
  • Isolated limb perfusion, ILP, is a standard of care for treating recurrent malignant melanoma confined to a limb.
  • Although an extracorporeal procedure, only a small percentage of perfusionists are experienced regarding ILP's indications and performance techniques.
  • Use of ILP may increase as the incidence of melanoma increases.
  • This two-part review is designed to familiarize the perfusionist with the procedure and the disease it treats.
  • Part I reviews the history of isolated limb perfusion, the diagnosis and classification of malignant melanoma, and the applicability of ILP in its treatment.
  • Part II details a procedural overview and technical considerations of the therapy from the perfusionist perspective.
  • The review concludes with patient selection, outcomes, and the future of ILP as well as other applications for the hyperthermic regional delivery of chemotherapy using extracorporeal technology.
  • [MeSH-major] Chemotherapy, Cancer, Regional Perfusion / methods. Melanoma / drug therapy. Skin Neoplasms / drug therapy
  • [MeSH-minor] Antineoplastic Agents / therapeutic use. Combined Modality Therapy. Extremities / pathology. Female. Humans. Hyperthermia, Induced. Male. Neoplasm Metastasis. Patient Selection. Recurrence. Survival Rate. Treatment Outcome

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  • (PMID = 12139123.001).
  • [ISSN] 0022-1058
  • [Journal-full-title] The journal of extra-corporeal technology
  • [ISO-abbreviation] J Extra Corpor Technol
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents
  • [Number-of-references] 52
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21. Lee HS, Song HH, Jeong JH, Shin CG, Choi SU, Lee C: Cytotoxicities of enniatins H, I, and MK1688 from Fusarium oxysporum KFCC 11363P. Toxicon; 2008 Jun 1;51(7):1178-85

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • Enniatins (ENs) H, I, and MK1688 and beauvericin (BEA) were purified from concentrated chloroform extracts of Fusarium oxysporum KFCC 11363P submerged cultures using HPLC, and their in vitro cytotoxicities were evaluated against four human carcinoma cell lines (lung, A549; ovarian, SK-OV-3; skin melanoma, SK-MEL-2; and colon, HCT15) using the sulforhodamine B (SRB) method.
  • ENs I and MK1688 inhibited the growth of cancer cell lines most strongly and had similar cytotoxic effects on the tested human cancer cell cultures.
  • The cytotoxicity of ENs I and MK1688 was three- to fourfold higher than that of BEA and EN H.
  • When cultivated in Fusarium-defined medium (FDM), the concentrations of ENs and BEA produced in F. oxysporum KFCC 11363P decreased in the following order: EN MK1688 (0.81 g/L) >EN I (0.55 g/L) >BEA (0.17 g/L) > EN H (0.16 g/L).
  • [MeSH-minor] Cell Line, Tumor / drug effects. Cell Survival / drug effects. Chromatography, High Pressure Liquid. Dose-Response Relationship, Drug. Drug Screening Assays, Antitumor. Humans. Neoplasms / drug therapy. Neoplasms / pathology

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  • (PMID = 18394672.001).
  • [ISSN] 0041-0101
  • [Journal-full-title] Toxicon : official journal of the International Society on Toxinology
  • [ISO-abbreviation] Toxicon
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Depsipeptides; 0 / enniatins; 26S048LS2R / beauvericin
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22. Bhattacharya N, Mukherjee KL, Chettri MK, Banerjee T, Bhattacharya S, Ghosh A, Bhattacharya M: A unique experience with human pre-immune (12 weeks) and hypo-immune (16 weeks) fetal thymus transplant in a vascular subcutaneous axillary fold in patients with advanced cancer: a report of two cases. Eur J Gynaecol Oncol; 2001;22(4):273-7
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  • [Title] A unique experience with human pre-immune (12 weeks) and hypo-immune (16 weeks) fetal thymus transplant in a vascular subcutaneous axillary fold in patients with advanced cancer: a report of two cases.
  • BACKGROUND: The successful development of fetal cell/tissue transplantation in adults has resulted in the possibility of eventual therapeutic solutions with a variety of intractable diseases.
  • Successful fetal tissue transplant in adults has raised the hope of future effective gene transplant and its manipulation prospects to combat many diseases including hemopathies, inborn errors of metabolism, immunodeficiencies and even cancer and AIDS.
  • MATERIALS AND METHOD: Two cases of advanced cancer were treated with fetal (pre-immune 12 weeks and hypo-immune 16 weeks) thymus transplants in subcutaneous vascular axillary folds, which were removed after one month.
  • RESULTS AND ANALYSIS: Patient I was suffering from non-Hodgkins lymphoma (Ann Arbor Stage IV) and was receiving cyclophosphomide, doxorubicin, vincristine and prednisolone after a course of radiotherapy; she developed leucopenia (2.400/cmm), which improved after receiving a 16-week human fetal thymic graft.
  • The leucopenia was eventually over-corrected and the leucocyte count reached 44,000/cmm within a month, which was reversed after the thymus was taken out.
  • Patient 2 was suffering from breast duct carcinoma (T4, N2, M0,) with estrogen, progesterone, and epidermal growth factor negative status, and was treated with modified radical mastectomy and axillary clearance followed by chemotherapy with cyclophosphomide, methotrexate and 5-fluorouracil for six cycles.
  • In this case the peripheral leucocyte count did not show appreciable variation as in the first case.
  • CONCLUSION: Pre-immune and hypo-immune human fetal thymic transplant is not rejected in patients suffering from advanced cancer within one month (observation period).
  • Thymic lymphocyte shedding in the correction of leucopenia in the background of non-Hodgkin's lymphoma may have many therapeutic implications.
  • [MeSH-major] Breast Neoplasms / therapy. Fetal Tissue Transplantation. Lymphoma, Non-Hodgkin / therapy. Thymus Gland / transplantation
  • [MeSH-minor] Adolescent. Adult. Axilla. Female. Humans. Leukopenia / etiology. Leukopenia / therapy. Lymphocyte Count

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  • (PMID = 11695808.001).
  • [ISSN] 0392-2936
  • [Journal-full-title] European journal of gynaecological oncology
  • [ISO-abbreviation] Eur. J. Gynaecol. Oncol.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Italy
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23. Jansen B, Wacheck V, Heere-Ress E, Schlagbauer-Wadl H, Hoeller C, Lucas T, Hoermann M, Hollenstein U, Wolff K, Pehamberger H: Chemosensitisation of malignant melanoma by BCL2 antisense therapy. Lancet; 2000 Nov 18;356(9243):1728-33
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Chemosensitisation of malignant melanoma by BCL2 antisense therapy.
  • BACKGROUND: Chemoresistance of malignant melanoma has been linked to expression of the proto-oncogene BCL2.
  • This phase I-II clinical study investigated the combination of BCL2 ASO (augmerosen, Genasense, G3139) and dacarbazine in patients with advanced malignant melanoma expressing BCL2.
  • METHODS: In a within-patient dose-escalation protocol, 14 patients with advanced malignant melanoma were given augmerosen intravenously or subcutaneously in daily doses of 0.6-6.5 mg/kg plus standard dacarbazine treatment (total doses up to 1000 mg/m2 per cycle).
  • By day 5, daily doses of 1.7 mg/kg and higher led to a median 40% decrease in BCL2 protein in melanoma samples compared with baseline, concomitantly with increased tumour-cell apoptosis, which was greatly increased after dacarbazine treatment.
  • INTERPRETATION: Systemic administration of augmerosen downregulated the target BCL2 protein in metastatic cancer.
  • Such downregulation of BCL2, combined with standard anticancer therapy, offers a new approach to the treatment of patients with resistant neoplasms.
  • [MeSH-major] DNA, Antisense / therapeutic use. Melanoma / drug therapy. Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Antineoplastic Agents, Alkylating / adverse effects. Antineoplastic Agents, Alkylating / therapeutic use. Dacarbazine / adverse effects. Dacarbazine / therapeutic use. Dose-Response Relationship, Drug. Drug Therapy, Combination. Female. Fever / chemically induced. Follow-Up Studies. Hematologic Diseases / chemically induced. Humans. Male. Middle Aged. Skin / drug effects. Skin / pathology. Skin Neoplasms / prevention & control. Skin Neoplasms / secondary. Survival Analysis. Treatment Outcome

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  • (PMID = 11095261.001).
  • [ISSN] 0140-6736
  • [Journal-full-title] Lancet (London, England)
  • [ISO-abbreviation] Lancet
  • [Language] eng
  • [Publication-type] Clinical Trial; Clinical Trial, Phase I; Clinical Trial, Phase II; Controlled Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] ENGLAND
  • [Chemical-registry-number] 0 / Antineoplastic Agents, Alkylating; 0 / DNA, Antisense; 0 / Proto-Oncogene Proteins c-bcl-2; 7GR28W0FJI / Dacarbazine
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24. Levy A, Guitera P, Kerob D, Ollivaud L, Archimbaud A, Dubertret L, Basset-Seguin N: [Hypersensitivity to dacarbazine in patients with metastatic malignant melanoma]. Ann Dermatol Venereol; 2006 Feb;133(2):157-60
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  • [Title] [Hypersensitivity to dacarbazine in patients with metastatic malignant melanoma].
  • [Transliterated title] Hypersensibilité à la dacarbazine chez les malades traités pour mélanome métastatique.
  • BACKGROUND: Dacarbazine (DTIC) is the first-line chemotherapy for metastatic malignant melanoma without cerebral metastasis.
  • PATIENTS AND METHODS: This was a retrospective study of the prevalence of hypersensitivity in patients treated with DTIC for metastatic melanoma between 11/01/2002 and 10/31/2003.
  • Hypersensitivity was diagnosed in the event of fever, hypereosinophilia (> 500/mm3) with or without liver dysfunction (> twice pre-therapeutic values).
  • Clinical data, DTIC administration modalities, number of courses and clinical and laboratory safety data were recorded.
  • DTIC was the first-line treatment for 19 patients, being administered for 4 days to 10 patients and for 1 day to the other 10 patients, depending on their overall health status.
  • Five hypersensitivity-like manifestations were observed, all in the 4-day treatment group.
  • In 3 patients, fever and hypereosinophilia were seen without liver dysfunction at D3 of the second course of treatment.
  • In 2 patients, treatment was stopped after the second course because of disease progression.
  • In the third patient, 4 courses were given with recurrence of symptoms, although the latter were controlled during the fifth course with corticosteroids and antihistamines given 15 minutes before the start of treatment.
  • Two patients experienced severe forms of hypersensitivity with fever, hypereosinophilia, liver dysfunction (cytolysis and cholestasis) and delayed medullar aplasia, after the first and second course respectively.
  • In one patient, bone marrow examination showed a block at the promyelocytic stage consistent with a toxic etiology.
  • Treatment with DTIC was stopped, and all signs regressed with symptomatic treatment.
  • DISCUSSION: Hypersensitivity with DTIC seems to be frequent, being observed in 20% of our patients, with early onset (after the first or second course) and absence of dose-dependence.
  • We describe for the first time two cases of medullar aplasia occurring in association with DTIC hypersensitivity.
  • During phase I studies, the hematologic toxicity of DTIC was moderate, rarely affecting red cells, and was observed with higher doses than those used in metastatic malignant melanoma.
  • CONCLUSION: Laboratory monitoring (NFS, liver enzymes) is thus justified, particularly after the first and second courses of DTIC.
  • In case of fever and hypereosinophilia without liver dysfunction, DTIC may be continued together with symptomatic treatment.
  • In the event of hepatic dysfunction, and of course severe hematological disorders, potentially fatal complications can occur and treatment must be stopped.
  • [MeSH-major] Antineoplastic Agents, Alkylating / adverse effects. Dacarbazine / adverse effects. Drug Hypersensitivity / etiology. Melanoma / drug therapy. Skin Neoplasms / drug therapy
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Anemia, Aplastic / chemically induced. Cross-Sectional Studies. Female. Humans. Lymphatic Metastasis. Male. Middle Aged. Neoplasm Metastasis. Retrospective Studies. Time Factors

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  • (PMID = 16508601.001).
  • [ISSN] 0151-9638
  • [Journal-full-title] Annales de dermatologie et de vénéréologie
  • [ISO-abbreviation] Ann Dermatol Venereol
  • [Language] fre
  • [Publication-type] English Abstract; Journal Article
  • [Publication-country] France
  • [Chemical-registry-number] 0 / Antineoplastic Agents, Alkylating; 7GR28W0FJI / Dacarbazine
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25. Wolchok JD, Williams L, Pinto JT, Fleisher M, Krown SE, Hwu WJ, Livingston PO, Chang C, Chapman PB: Phase I trial of high dose paracetamol and carmustine in patients with metastatic melanoma. Melanoma Res; 2003 Apr;13(2):189-96
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Phase I trial of high dose paracetamol and carmustine in patients with metastatic melanoma.
  • We conducted a phase I trial of high dose paracetamol and carmustine (BCNU) in patients with advanced malignant melanoma to determine the optimal biological dose and the maximum tolerated dose (MTD) with the goal of increasing sensitivity to BCNU by GSH depletion.
  • Every other cycle, BCNU (10 mg/m(2)) was given 6.5 h after administration of paracetamol and 45 min before a 20 h infusion of N-acetylcysteine.
  • Treatment of melanoma patients with paracetamol (15 g/m(2)) every 3 weeks and BCNU (150 mg/m(2)) every 6 weeks is safe.
  • The observation of two partial responses has led to a phase II study to evaluate treatment with high dose paracetamol alone or in combination with BCNU.
  • [MeSH-major] Acetaminophen / therapeutic use. Carmustine / therapeutic use. Melanoma / drug therapy
  • [MeSH-minor] Acetylcysteine / therapeutic use. Analgesics, Non-Narcotic / therapeutic use. Antineoplastic Agents, Alkylating / therapeutic use. Cohort Studies. Dose-Response Relationship, Drug. Female. Free Radical Scavengers / therapeutic use. Glutathione / metabolism. Glutathione Reductase / metabolism. Humans. Leukocytes, Mononuclear / metabolism. Liver Neoplasms / pathology. Lymphatic Metastasis. Male. Maximum Tolerated Dose. Neoplasm Metastasis. Skin Neoplasms / pathology. Time Factors

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  • (PMID = 12690304.001).
  • [ISSN] 0960-8931
  • [Journal-full-title] Melanoma research
  • [ISO-abbreviation] Melanoma Res.
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / CA05826; United States / NCI NIH HHS / CA / CA81293
  • [Publication-type] Clinical Trial; Clinical Trial, Phase I; Journal Article; Research Support, U.S. Gov't, P.H.S.
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Analgesics, Non-Narcotic; 0 / Antineoplastic Agents, Alkylating; 0 / Free Radical Scavengers; 362O9ITL9D / Acetaminophen; EC 1.8.1.7 / Glutathione Reductase; GAN16C9B8O / Glutathione; U68WG3173Y / Carmustine; WYQ7N0BPYC / Acetylcysteine
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26. Thompson JA, Curti BD, Redman BG, Bhatia S, Weber JS, Agarwala SS, Sievers EL, Hughes SD, DeVries TA, Hausman DF: Phase I study of recombinant interleukin-21 in patients with metastatic melanoma and renal cell carcinoma. J Clin Oncol; 2008 Apr 20;26(12):2034-9
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Phase I study of recombinant interleukin-21 in patients with metastatic melanoma and renal cell carcinoma.
  • PURPOSE: A phase I study of patients with metastatic malignant melanoma (MM) and renal cell carcinoma (RCC) evaluated the safety and maximum tolerated dose (MTD), pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of recombinant human interleukin-21 (rIL-21).
  • PATIENTS AND METHODS: Patients who had one or fewer prior systemic treatments for metastatic MM or RCC were treated with rIL-21 administered for two 5-day cycles on days 1 through 5 and 15 through 19 of a treatment course; rIL-21 was administered by rapid intravenous infusion in an outpatient setting.
  • Patients with stable disease (SD) or better could receive additional treatment cycles.
  • Twelve patients received up to five additional two-cycle courses of treatment without cumulative toxicity, except for one patient with reversible grade 4 hepatotoxicity.
  • CONCLUSION: Outpatient therapy with rIL-21 at 30 microg/kg was well tolerated, had dose-dependent pharmacokinetics and pharmacodynamics, and was associated with antitumor activity in patients with MM and RCC.
  • [MeSH-major] Carcinoma, Renal Cell / therapy. Interleukins / administration & dosage. Interleukins / adverse effects. Kidney Neoplasms / therapy. Melanoma / therapy
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Dose-Response Relationship, Drug. Female. Humans. Immunotherapy / methods. Male. Middle Aged. Neoplasm Metastasis. Recombinant Proteins / administration & dosage. Recombinant Proteins / adverse effects. Recombinant Proteins / pharmacokinetics

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  • (PMID = 18347008.001).
  • [ISSN] 1527-7755
  • [Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • [ISO-abbreviation] J. Clin. Oncol.
  • [Language] eng
  • [Publication-type] Clinical Trial, Phase I; Journal Article; Multicenter Study
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Interleukins; 0 / Recombinant Proteins; 0 / interleukin-21
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27. López M, Aguilera R, Pérez C, Mendoza-Naranjo A, Pereda C, Ramirez M, Ferrada C, Aguillón JC, Salazar-Onfray F: The role of regulatory T lymphocytes in the induced immune response mediated by biological vaccines. Immunobiology; 2006;211(1-2):127-36

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • Immunotherapy has become a novel therapeutic alternative for various kinds of tumours.
  • Recently, we have finalized the first phase I clinical study in Chile for the treatment of advanced malignant melanoma, using dendritic cells (DCs) loaded with allogeneic melanoma cell lysate.
  • In addition, immunological responses were detected in 50% of the treated patients, establishing a positive correlation between the delayed type hypersensitivity (DTH) reaction, which indicates induction of in vivo immunological memory, and patients surviving.
  • Actually, we have demonstrated that IL-10 inhibits antigen presentation in melanoma, reducing tumour sensitivity to melanoma-specific cytotoxic T lymphocytes (CTLs).
  • In relation to RTL and cancer, evidence indicates that Treg cell numbers are increased in blood and other tissues in different types of cancer.
  • Additionally, it has been demonstrated that in patients with refractory metastatic melanoma, the adoptive transference of anti-tumour CD8+ T lymphocytes after non-myeloablative chemotherapy was able to induce important tumour regressions that would be due to elimination of RTL populations.
  • Additionally, chemotherapeutical drugs like decarbazine, besides their effect on tumour proliferation, also have an immunosuppressive effect on T lymphocyte populations, as well as on accumulated RTL.
  • In this article, a novel strategy for the study of RTL is proposed, including potential therapeutic innovations, which is being pioneered in current clinical trials.
  • [MeSH-major] Cancer Vaccines / immunology. Neoplasms. T-Lymphocytes, Regulatory / immunology
  • [MeSH-minor] Animals. Biomarkers, Tumor / analysis. Biomarkers, Tumor / secretion. Clinical Trials, Phase I as Topic. Dendritic Cells / immunology. Dendritic Cells / transplantation. Humans. Immunotherapy, Adoptive / methods. Immunotherapy, Adoptive / trends

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  • (PMID = 16446177.001).
  • [ISSN] 0171-2985
  • [Journal-full-title] Immunobiology
  • [ISO-abbreviation] Immunobiology
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't; Review
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / Biomarkers, Tumor; 0 / Cancer Vaccines
  • [Number-of-references] 53
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28. Wong SF, Jakowatz JG, Taheri R: Potential drug-drug interaction between interferon alfa-2b and gemfibrozil in a patient with malignant melanoma. Clin Ther; 2005 Dec;27(12):1942-8
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  • [Title] Potential drug-drug interaction between interferon alfa-2b and gemfibrozil in a patient with malignant melanoma.
  • BACKGROUND: In the United States, patients with high-risk stage II or III melanoma are often treated with adjuvant interferon (IFN) therapy for 1 year after surgery.
  • However, hypertriglyceridemia requiring treatment has been reported.
  • OBJECTIVE: The aim of this report was to describe a potential drug-drug interaction between IFN alfa-2b and gemfibrozil in a patient with malignant melanoma.
  • METHODS: This report presents the case of a 43-year-old male patient weighing 101 kg with newly diagnosed stage III melanoma of the left arm, with metastasis to the supraclavicular node.
  • The patient presented to the University of California Irvine Medical Center, Orange, California with severe gastrointestinal (GI) symptoms and elevated hepatic enzyme concentrations at week 48 of 104 of adjuvant treatment of malignant melanoma (IFN alfa 11 MU SC TIW in combination with the investigational melanoma vaccine melanoma theraccine 1.25 mL [I mL lysate + 0.25 mL vaccine adjuvant] given SC at weeks 1, 2, 3, 4, 8, 16, 24, 32, 40, and 48 and then every 8 weeks until week 104), and IFN-induced hypertriglyceridemia (gemfibrozil 600 mg PO BID).
  • The patient had no history of cardiovascular or GI disease and was not receiving any concomitant medication.
  • RESULTS: In this case of a possible drug-drug interaction between IFN alfa 11 MU TIW and gemfibrozil 600 mg BID in a patient undergoing treatment for IFN-induced hypertriglyceridemia, the Naranjo Adverse Drug Reactions (ADR) Probability Scale score was 7 (ie, ADR possibly related to treatment).
  • A possible drug-drug interaction between IFN alfa 11 MU TIW and gemfibrozil 600 mg BID was reported in a patient undergoing treatment for IFN-induced hypertriglyceridemia.
  • [MeSH-major] Antineoplastic Agents / adverse effects. Gemfibrozil / adverse effects. Hypertriglyceridemia / drug therapy. Hypolipidemic Agents / adverse effects. Interferon-alpha / adverse effects
  • [MeSH-minor] Adult. Chemotherapy, Adjuvant / adverse effects. Drug Interactions. Humans. Lymphatic Metastasis. Male. Melanoma / drug therapy. Recombinant Proteins. Skin Neoplasms / drug therapy

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  • (PMID = 16507380.001).
  • [ISSN] 0149-2918
  • [Journal-full-title] Clinical therapeutics
  • [ISO-abbreviation] Clin Ther
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Hypolipidemic Agents; 0 / Interferon-alpha; 0 / Recombinant Proteins; 99210-65-8 / interferon alfa-2b; Q8X02027X3 / Gemfibrozil
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29. Alatrash G, Hutson TE, Molto L, Richmond A, Nemec C, Mekhail T, Elson P, Tannenbaum C, Olencki T, Finke J, Bukowski RM: Clinical and immunologic effects of subcutaneously administered interleukin-12 and interferon alfa-2b: phase I trial of patients with metastatic renal cell carcinoma or malignant melanoma. J Clin Oncol; 2004 Jul 15;22(14):2891-900
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  • [Title] Clinical and immunologic effects of subcutaneously administered interleukin-12 and interferon alfa-2b: phase I trial of patients with metastatic renal cell carcinoma or malignant melanoma.
  • PURPOSE: Interleukin-12 (IL-12) and interferon alfa-2b (IFN-alpha-2b) are pleiotropic cytokines with activity in renal cell carcinoma (RCC) and malignant melanoma (MM) as single agents.
  • PATIENTS AND METHODS: Cohorts of three to six patients were treated with escalating doses of IL-12 (dose I, 100 ng/kg; dose II, 300 ng/kg; dose III, 500 ng/kg; dose IV, 500 ng/kg SC) given twice weekly and IFN-alpha-2b (dose I, 1.0 MU/m(2); dose II, 1.0 MU/m(2); dose III, 1.0 MU/m(2); dose IV, 3.0 MU/m(2) SC) three times weekly in 4-week cycles.
  • Patients received a median of three cycles of treatment.
  • [MeSH-major] Antineoplastic Agents / administration & dosage. Carcinoma, Renal Cell / drug therapy. Interferon-alpha / administration & dosage. Interleukin-12 / administration & dosage. Kidney Neoplasms / drug therapy. Melanoma / drug therapy. Skin Neoplasms / drug therapy
  • [MeSH-minor] Adult. Aged. Cytokines / genetics. Cytokines / immunology. Drug Administration Schedule. Female. Gene Expression. Humans. Injections, Subcutaneous. Male. Maximum Tolerated Dose. Middle Aged. Recombinant Proteins. Treatment Outcome

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  • (PMID = 15254058.001).
  • [ISSN] 0732-183X
  • [Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • [ISO-abbreviation] J. Clin. Oncol.
  • [Language] eng
  • [Publication-type] Clinical Trial; Clinical Trial, Phase I; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Cytokines; 0 / Interferon-alpha; 0 / Recombinant Proteins; 187348-17-0 / Interleukin-12; 99210-65-8 / interferon alfa-2b
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30. Green DS, Bodman-Smith MD, Dalgleish AG, Fischer MD: Phase I/II study of topical imiquimod and intralesional interleukin-2 in the treatment of accessible metastases in malignant melanoma. Br J Dermatol; 2007 Feb;156(2):337-45
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Phase I/II study of topical imiquimod and intralesional interleukin-2 in the treatment of accessible metastases in malignant melanoma.
  • BACKGROUND: Patients with metastatic skin disease in malignant melanoma can be difficult to treat effectively, often requiring repeated treatments with different modalities in an attempt to control their disease.
  • Treatment of nonsurgically resectable melanoma deposits is unsatisfactory, as they are often multiple and recurring.
  • OBJECTIVES: To investigate the combination of topical imiquimod and, for selected lesions, intralesional IL-2, to treat a small cohort of patients with accessible melanoma metastases resistant to other treatments.
  • METHODS: Thirteen patients were recruited: all had evidence of multiple cutaneous and/or subcutaneous metastases.
  • This was injected up to three times a week, into selected lesions, with 0.1 mL injected per lesion at a concentration of 3.6 MIU mL(-1), a total of 1 mL being given at each session.
  • In total, 182 lesions were treated: 137 purely cutaneous lesions and 41 subcutaneous lesions.
  • Overall, a clinical response was seen in 92 lesions (50.5%) with 74 (40.7%) of these being a complete response (CR) with 91% of the CRs being in the cutaneous lesions.
  • New lesions did appear during the treatment course; however, patients with cutaneous disease experienced a marked slowing of the appearance of new cutaneous lesions.
  • No cutaneous lesions that responded reappeared on cessation of treatment.
  • CONCLUSIONS: The combination of imiquimod and IL-2 is effective in controlling this mixed cutaneous and subcutaneous disease, and is well tolerated.
  • Imiquimod alone is often enough to elicit a response in purely cutaneous lesions.
  • The addition of intralesional IL-2 increases the response rates in subcutaneous lesions, and in otherwise refractory cutaneous lesions.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Melanoma / drug therapy. Neoplasm Recurrence, Local / drug therapy. Skin Neoplasms / drug therapy
  • [MeSH-minor] Administration, Cutaneous. Aged. Aged, 80 and over. Aminoquinolines / administration & dosage. Dose-Response Relationship, Drug. Female. Humans. Injections, Intralesional. Interleukin-2 / administration & dosage. Male. Middle Aged. Ointments. Treatment Outcome

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  • (PMID = 17223875.001).
  • [ISSN] 0007-0963
  • [Journal-full-title] The British journal of dermatology
  • [ISO-abbreviation] Br. J. Dermatol.
  • [Language] eng
  • [Publication-type] Clinical Trial, Phase I; Clinical Trial, Phase II; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Aminoquinolines; 0 / Interleukin-2; 0 / Ointments; 99011-02-6 / imiquimod
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31. Larkin JM, Hughes SA, Beirne DA, Patel PM, Gibbens IM, Bate SC, Thomas K, Eisen TG, Gore ME: A phase I/II study of lomustine and temozolomide in patients with cerebral metastases from malignant melanoma. Br J Cancer; 2007 Jan 15;96(1):44-8
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  • [Title] A phase I/II study of lomustine and temozolomide in patients with cerebral metastases from malignant melanoma.
  • Temozolomide is an alkylating agent with activity in the treatment of melanoma metastatic to the brain.
  • A multicentre phase I/II study was conducted to assess the maximum-tolerated dose (MTD), safety and efficacy of the combination of temozolomide and lomustine in melanoma metastatic to the brain.
  • No responses to therapy were observed.
  • Median survival from starting chemotherapy was 2 months.
  • The combination of temozolomide and lomustine in patients with brain metastases from melanoma does not demonstrate activity.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Brain Neoplasms / drug therapy. Dacarbazine / analogs & derivatives. Lomustine / administration & dosage. Melanoma / drug therapy
  • [MeSH-minor] Administration, Oral. Adult. Dose-Response Relationship, Drug. Drug Administration Schedule. Female. Follow-Up Studies. Humans. Male. Maximum Tolerated Dose. Middle Aged. Neutropenia / chemically induced. Thrombocytopenia / chemically induced. Treatment Failure

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  • (PMID = 17146474.001).
  • [ISSN] 0007-0920
  • [Journal-full-title] British journal of cancer
  • [ISO-abbreviation] Br. J. Cancer
  • [Language] eng
  • [Publication-type] Clinical Trial, Phase I; Clinical Trial, Phase II; Journal Article; Multicenter Study
  • [Publication-country] England
  • [Chemical-registry-number] 7BRF0Z81KG / Lomustine; 7GR28W0FJI / Dacarbazine; 85622-93-1 / temozolomide
  • [Other-IDs] NLM/ PMC2360201
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32. Cebon J, Jäger E, Shackleton MJ, Gibbs P, Davis ID, Hopkins W, Gibbs S, Chen Q, Karbach J, Jackson H, MacGregor DP, Sturrock S, Vaughan H, Maraskovsky E, Neumann A, Hoffman E, Sherman ML, Knuth A: Two phase I studies of low dose recombinant human IL-12 with Melan-A and influenza peptides in subjects with advanced malignant melanoma. Cancer Immun; 2003 Jul 16;3:7
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  • [Title] Two phase I studies of low dose recombinant human IL-12 with Melan-A and influenza peptides in subjects with advanced malignant melanoma.
  • Subjects had evaluable stage III or IV melanoma which expressed Melan-A by RT-PCR or immunohistochemistry.
  • Therapy was well tolerated, the main adverse event being influenza-like symptoms.
  • Immunological monitoring included the evaluation of cutaneous reactions and assays for antigen-specific T-cells.
  • [MeSH-major] Interleukin-12 / therapeutic use. Melanoma / drug therapy. Neoplasm Proteins / therapeutic use. Peptide Fragments / therapeutic use. Recombinant Proteins / therapeutic use. Viral Matrix Proteins / therapeutic use
  • [MeSH-minor] Adjuvants, Immunologic / therapeutic use. Adolescent. Adult. Aged. Antigens, Neoplasm / adverse effects. Antigens, Neoplasm / therapeutic use. Cancer Vaccines / adverse effects. Cancer Vaccines / therapeutic use. Drug Administration Schedule. Drug Hypersensitivity. Drug Therapy, Combination. Female. Humans. Influenza A virus / chemistry. Injections, Intravenous. Injections, Subcutaneous. MART-1 Antigen. Male. Middle Aged

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  • (PMID = 12862418.001).
  • [ISSN] 1424-9634
  • [Journal-full-title] Cancer immunity
  • [ISO-abbreviation] Cancer Immun.
  • [Language] eng
  • [Publication-type] Clinical Trial; Clinical Trial, Phase I; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Adjuvants, Immunologic; 0 / Antigens, Neoplasm; 0 / Cancer Vaccines; 0 / MART-1 Antigen; 0 / MLANA protein, human; 0 / Neoplasm Proteins; 0 / Peptide Fragments; 0 / Recombinant Proteins; 0 / Viral Matrix Proteins; 0 / influenza virus membrane protein (58-66); 187348-17-0 / Interleukin-12
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33. Bartlett JB, Michael A, Clarke IA, Dredge K, Nicholson S, Kristeleit H, Polychronis A, Pandha H, Muller GW, Stirling DI, Zeldis J, Dalgleish AG: Phase I study to determine the safety, tolerability and immunostimulatory activity of thalidomide analogue CC-5013 in patients with metastatic malignant melanoma and other advanced cancers. Br J Cancer; 2004 Mar 8;90(5):955-61
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  • [Title] Phase I study to determine the safety, tolerability and immunostimulatory activity of thalidomide analogue CC-5013 in patients with metastatic malignant melanoma and other advanced cancers.
  • We assessed the safety, tolerability and efficacy of the immunomodulatory drug, CC-5013 (REVIMID trade mark ), in the treatment of patients with metastatic malignant melanoma and other advanced cancers.
  • In all, 87% of adverse effects were classified as grade 1 or grade 2 according to Common Toxicity Criteria and there were no serious adverse events attributable to CC-5013 treatment.
  • The remaining 14 patients completed treatment without dose reduction, with one patient achieving partial remission.
  • Evidence of T-cell activation was indicated by significantly increased serum levels of sIL-2 receptor, granulocyte-macrophage colony-stimulating factor, interleukin-12 (IL-12), tumour necrosis factor-alpha and IL-8 in nine patients from whom serum was available.
  • This study demonstrates the safety, tolerability and suggests the clinical activity of CC-5013 in the treatment of refractory malignant melanoma.
  • Furthermore, this is the first report demonstrating T-cell stimulatory activity of this class of compound in patients with advanced cancer.
  • [MeSH-major] Angiogenesis Inhibitors / therapeutic use. Melanoma / drug therapy. Skin Neoplasms / drug therapy. Thalidomide / analogs & derivatives. Thalidomide / therapeutic use
  • [MeSH-minor] Adolescent. Adult. Aged. Aged, 80 and over. Cytokines / blood. Female. Fibroblast Growth Factor 2 / metabolism. Humans. Immunization. Male. Maximum Tolerated Dose. Middle Aged. Neoplasms / drug therapy. Neoplasms / pathology. Safety. T-Lymphocytes / metabolism. Vascular Endothelial Growth Factor A / metabolism

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  • (PMID = 14997189.001).
  • [ISSN] 0007-0920
  • [Journal-full-title] British journal of cancer
  • [ISO-abbreviation] Br. J. Cancer
  • [Language] eng
  • [Publication-type] Clinical Trial; Clinical Trial, Phase I; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Angiogenesis Inhibitors; 0 / Cytokines; 0 / Vascular Endothelial Growth Factor A; 103107-01-3 / Fibroblast Growth Factor 2; 4Z8R6ORS6L / Thalidomide; F0P408N6V4 / lenalidomide
  • [Other-IDs] NLM/ PMC2410215
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34. Gollob JA, Mier JW, Veenstra K, McDermott DF, Clancy D, Clancy M, Atkins MB: Phase I trial of twice-weekly intravenous interleukin 12 in patients with metastatic renal cell cancer or malignant melanoma: ability to maintain IFN-gamma induction is associated with clinical response. Clin Cancer Res; 2000 May;6(5):1678-92
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  • [Title] Phase I trial of twice-weekly intravenous interleukin 12 in patients with metastatic renal cell cancer or malignant melanoma: ability to maintain IFN-gamma induction is associated with clinical response.
  • Stable or responding patients were eligible to receive additional 6-week cycles until there was no evidence of disease or until tumor progression.
  • At the MTD (n = 14), there was one partial response occurring after 6 cycles of rhIL-12 in a patient with renal cell cancer.
  • Two additional renal cell cancer patients treated at the MTD had prolonged disease stabilization, with one of these exhibiting tumor regression after 8 cycles of rhIL-12.
  • Whereas IFN-gamma and IL-15 induction were attenuated midway through the first cycle in patients with disease progression, those patients with tumor regression or prolonged disease stabilization were able to maintain IFN-gamma, IL-15, and IL-18 induction.
  • The down-modulation of IFN-gamma induction during rhIL-12 treatment did not relate to IL-10 production or alterations in rhIL-12 bioavailability but was associated with an acquired defect in lymphocyte IFN-gamma production in response to IL-12, IL-2, or IL-15.
  • These findings show that the chronic administration of twice-weekly i.v. rhIL-12 is well-tolerated, stimulates the production of IL-12 costimulatory cytokines and IFN-gamma, and can induce delayed tumor regression.
  • [MeSH-major] Carcinoma, Renal Cell / drug therapy. Interleukin-12 / therapeutic use. Kidney Neoplasms / drug therapy. Melanoma / drug therapy
  • [MeSH-minor] Adult. Aged. Arthralgia / chemically induced. Dose-Response Relationship, Drug. Female. Fever / chemically induced. Hematologic Diseases / chemically induced. Humans. Hypotension / chemically induced. Injections, Intravenous. Interferon-gamma / drug effects. Interferon-gamma / metabolism. Interleukin-15 / metabolism. Interleukin-18 / metabolism. Male. Middle Aged. Mouth Mucosa. Neoplasm Metastasis. Recombinant Proteins / adverse effects. Recombinant Proteins / pharmacokinetics. Recombinant Proteins / therapeutic use. Skin / drug effects. Skin / pathology. Stomatitis / chemically induced. Time Factors

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  • (PMID = 10815886.001).
  • [ISSN] 1078-0432
  • [Journal-full-title] Clinical cancer research : an official journal of the American Association for Cancer Research
  • [ISO-abbreviation] Clin. Cancer Res.
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / CA 78055; United States / NCI NIH HHS / CA / CA74401
  • [Publication-type] Clinical Trial; Clinical Trial, Phase I; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.
  • [Publication-country] UNITED STATES
  • [Chemical-registry-number] 0 / Interleukin-15; 0 / Interleukin-18; 0 / Recombinant Proteins; 187348-17-0 / Interleukin-12; 82115-62-6 / Interferon-gamma
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35. Sondak VK: Adjuvant therapy for melanoma. Cancer J; 2001 Jul-Aug;7 Suppl 1:S24-7
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  • [Title] Adjuvant therapy for melanoma.
  • Patients with deep primaries (> or = 4 mm) or regional lymph node involvement often require adjuvant therapy in addition to surgery to successfully treat melanoma.
  • Randomized trials of IFN-alpha adjuvant therapy have demonstrated statistically significant improvements in disease-free and overall survival rates, leading to approval by the United States Food and Drug Administration of the use of 1 year of intensive IFN-alpha2b following surgical resection of high-risk disease.
  • A study comparing high-dose IFN with the ganglioside vaccine GMK was terminated early when the Data Safety Monitoring Committee concluded that the high-dose IFN treatment arm was associated with highly significantly improved relapse-free and overall survival.
  • Studies of IFN-alpha in stage I and II melanoma are reviewed.
  • In addition to adjuvant therapy with IFN-alpha, various other treatment strategies appear promising.
  • Adjuvant vaccine therapy may be useful for treatment of cutaneous melanoma.
  • Polyvalent melanoma vaccines are discussed as a potential adjuvant therapy.
  • Finally, nonrandomized preliminary studies suggest that postoperative radiation to the neck or axilla after radical lymph node dissection may decrease regional recurrence rates in node-positive patients, supporting the selective use of radiation therapy for melanoma.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Melanoma / drug therapy. Melanoma / radiotherapy. Skin Neoplasms / drug therapy. Skin Neoplasms / radiotherapy
  • [MeSH-minor] Cancer Vaccines / therapeutic use. Chemotherapy, Adjuvant. Humans. Interferon-alpha / therapeutic use. Interferon-gamma / therapeutic use. Radiotherapy, Adjuvant

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  • (PMID = 11504282.001).
  • [ISSN] 1528-9117
  • [Journal-full-title] Cancer journal (Sudbury, Mass.)
  • [ISO-abbreviation] Cancer J
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Cancer Vaccines; 0 / Interferon-alpha; 82115-62-6 / Interferon-gamma
  • [Number-of-references] 35
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36. Petrescu I, Condrea C, Alexandru A, Dumitrescu D, Simion G, Severin E, Albu C, Albu D: Diagnosis and treatment protocols of cutaneous melanoma: latest approach 2010. Chirurgia (Bucur); 2010 Sep-Oct;105(5):637-43
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  • [Title] Diagnosis and treatment protocols of cutaneous melanoma: latest approach 2010.
  • Cutaneous melanoma is the most aggressive skin malignancies with increasing rate of incidence in the latest decades.
  • New imaging technique plays an important role in melanoma management: dermoscopy and computer dermoscopy, ultrasound, MRI, CT, PET and PET/CT.
  • Due to the dermoscopy and lesion diagnosis in early stages the increasing number of curative melanoma are registered.
  • Sentinel lymph node biopsy became a compulsory phase for patients with tumor thickness > 1 mm.
  • Serological biomarkers proved to be a necessary investigation for melanoma diagnosis, follow-up and treatment response.
  • Current TNM melanoma staging is based on AJCC classification since 2001 witch includes new elements like histopathologic ulceration in stage I and II and lymph node micro- and macrometastases in stage III.
  • Treatment protocols include surgical tumor excision with only 1-2 cm safety margins and radical lymphadenectomy is performed after positive sentinel lymph node biopsy.
  • The adjuvant treatment in advanced stages including chemotherapy, unspecific immunotherapy and interferon offers poor results regarding free disease terms rate of survival.
  • The advanced therapeutic procedure like golden nanospheres and gene therapy are recently studied and represent an alternative for future treatment of melanoma.
  • Follow-up protocols have a great importance for detection of the melanoma recurrences and include clinical, serological and imaging evaluation.
  • Despite all new knowledge and technological support the advanced stage melanoma management still remain an unsolved problem.
  • [MeSH-major] Melanoma / diagnosis. Melanoma / therapy. Skin Neoplasms / diagnosis. Skin Neoplasms / therapy
  • [MeSH-minor] Chemotherapy, Adjuvant. Diagnosis, Differential. Early Detection of Cancer. Humans. Incidence. Medical Oncology / trends. Neoplasm Staging. Risk Factors. Romania / epidemiology. Sentinel Lymph Node Biopsy. Survival Rate. Treatment Outcome

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  • (PMID = 21141087.001).
  • [ISSN] 1221-9118
  • [Journal-full-title] Chirurgia (Bucharest, Romania : 1990)
  • [ISO-abbreviation] Chirurgia (Bucur)
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] Romania
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37. Wang Y, Cen Y, Li Z: [Therapeutic result of operation combined with large-dose of roferon-A for cutaneous malignant melanoma]. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi; 2007 Jan;21(1):37-9
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  • [Title] [Therapeutic result of operation combined with large-dose of roferon-A for cutaneous malignant melanoma].
  • OBJECTIVE: To observe the effects of operation with large-dose of Roferon-A for cutaneous malignant melanoma.
  • METHODS: From January 1998 to December 2005, thirty-three patients with cutaneous malignant melanoma were treated.
  • In 33 patients, nine patients identified as clinical-stage I received singly enlarged-resection to the primary lesion and performed split-thickness skin graft dermoplasty or adjacent skin flap repair; twenty-three patients identified as clinical-stage II received enlarged-resection to the primary lesion and performed proximal lymphaden scavenge as well as received split-thickness skin graft dermoplasty; and one patient identified as clinical-stage III received palliative resection to the primary lesion.
  • RESULTS: There are no recidivation in the 9 patients of clinical-stage I.
  • There are 1 recidivation and 1 quit in all the 23 patients of clinical-stage II.
  • One patient of clinical-stage III died after 18 months of operation.
  • CONCLUSION: The operation combined with large-dose of Roferon-A after operation was a more effective way to treat cutaneous malignant melanoma.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Interferon-alpha / therapeutic use. Melanoma / drug therapy. Melanoma / surgery. Skin Neoplasms / drug therapy. Skin Neoplasms / surgery
  • [MeSH-minor] Adolescent. Adult. Aged. Female. Follow-Up Studies. Head and Neck Neoplasms / drug therapy. Head and Neck Neoplasms / pathology. Head and Neck Neoplasms / surgery. Humans. Injections, Intramuscular. Male. Middle Aged. Neoplasm Staging. Recombinant Proteins. Skin Transplantation. Surgical Flaps. Treatment Outcome. Young Adult

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  • (PMID = 17305002.001).
  • [ISSN] 1002-1892
  • [Journal-full-title] Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery
  • [ISO-abbreviation] Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi
  • [Language] chi
  • [Publication-type] English Abstract; Journal Article
  • [Publication-country] China
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Interferon-alpha; 0 / Recombinant Proteins; 76543-88-9 / interferon alfa-2a
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38. Tas F, Yasasever V, Duranyildiz D, Camlica H, Ustuner Z, Aydiner A, Topuz E: Clinical value of protein S100 and melanoma-inhibitory activity (MIA) in malignant melanoma. Am J Clin Oncol; 2004 Jun;27(3):225-8
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  • [Title] Clinical value of protein S100 and melanoma-inhibitory activity (MIA) in malignant melanoma.
  • Serum protein S100 and melanoma-inhibitory protein (MIA) have been described as useful tumor markers for malignant melanoma.
  • In this study, these two serum proteins were compared in 48 patients with melanoma at different stages of disease.
  • We found that the cut-off values were 17.4 ng/ml for MIA and 0.09 microg/l for S100.
  • Five patients had stage I-II, 22 had stage III, and 21 had stage IV disease.
  • Sensitivities of the MIA were found higher compared with S100 in patients with extensive (M1c) metastatic disease and with chemotherapy nonresponders (p > 0.05).
  • We showed a trend for worsened outcome in patients with elevated MIA level in univariate analysis.
  • MIA was found to be more sensitive and is a potential prognostic marker for patients with metastatic malignant melanoma in comparison with S100.
  • [MeSH-major] Biomarkers, Tumor / blood. Melanoma / blood. Neoplasm Proteins / blood. S100 Proteins / blood
  • [MeSH-minor] Adult. Aged. Extracellular Matrix Proteins. Female. Humans. Male. Middle Aged. Neoplasm Staging. Survival Analysis

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  • (PMID = 15170138.001).
  • [ISSN] 1537-453X
  • [Journal-full-title] American journal of clinical oncology
  • [ISO-abbreviation] Am. J. Clin. Oncol.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Biomarkers, Tumor; 0 / Extracellular Matrix Proteins; 0 / MIA protein, human; 0 / Neoplasm Proteins; 0 / S100 Proteins
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39. Fujii K, Goto A, Matsunaga Y, Hasegawa Y, Sukawa Y, Suzuki K, Yonezawa K, Abe T, Itoh A, Shinomura Y, Iimura Y, Hasegawa N, Nakamura H, Yoshida Y: [Primary malignant melanoma of the esophagus--detection of circulating tumor cells]. Gan To Kagaku Ryoho; 2010 Aug;37(8):1539-43
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  • [Title] [Primary malignant melanoma of the esophagus--detection of circulating tumor cells].
  • Primary malignant melanoma of esophagus (PMME) is a rare tumor; therefore, the prognostic factors, predictive factors, and difference in biological behaviors of cutaneous melanoma and primary esophageal squamous cell carcinoma remain uncertain.
  • Although we did not adopt a standard therapeutic strategy, we performed surgical resection, chemotherapy, immunotherapy, and radiotherapy either alone or in combination; all procedures resulted in poor outcomes.
  • A 67-year-old woman presented with a swallowing disorder.
  • An esophagogastroduodenoscopy was performed, leading to diagnosis of PMME.
  • According to the Japanese Classification of Esophageal Cancer, the pathological stage was T1b, ly0, v0, N0, M0, stage I .
  • After subtotal esophagectomy, adjuvant chemotherapy was performed, but the malignant melanoma relapsed in the mediastinum and the patient died 10 months after diagnosis.
  • We serially monitored the patient using several new modalities, including PET/CT, metabolites of melanin: 5-S-CD, and circulating tumor cells (CTCs) by reverse transcription-polymerase chain reaction to identify the melanoma-specific gene.
  • To our knowledge, this is the first report of a case in which CTCs in PMME were detected.
  • [MeSH-major] Esophageal Neoplasms / pathology. Melanoma / pathology. Neoplastic Cells, Circulating
  • [MeSH-minor] Aged. Biopsy. Fatal Outcome. Female. Gene Expression Regulation, Neoplastic. Humans. Recurrence. Tomography, X-Ray Computed

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  • (PMID = 20716882.001).
  • [ISSN] 0385-0684
  • [Journal-full-title] Gan to kagaku ryoho. Cancer & chemotherapy
  • [ISO-abbreviation] Gan To Kagaku Ryoho
  • [Language] jpn
  • [Publication-type] Case Reports; English Abstract; Journal Article
  • [Publication-country] Japan
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40. Stahlecker J, Gauger A, Bosserhoff A, Büttner R, Ring J, Hein R: MIA as a reliable tumor marker in the serum of patients with malignant melanoma. Anticancer Res; 2000 Nov-Dec;20(6D):5041-4
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  • [Title] MIA as a reliable tumor marker in the serum of patients with malignant melanoma.
  • BACKGROUND: Reports published in 1996 concerning the protein MIA proposed it as a useful tumor marker for patients suffering from malignant melanoma.
  • Therefore we systematically started to measure MIA levels in patients with malignant melanoma.
  • It was and still is questionable whether MIA in the serum of melanoma patients is a reliable tumor marker in terms of course of disease, therapy-monitoring and prognostic value.
  • Previous studies have already confirmed the specifity of MIA as a tumor marker for malignant melanoma.
  • MATERIALS AND METHODS: Using an ELISA- System, we examined over 830 blood samples of 326 melanoma patients.
  • The cut-off was determined at 9.8 ng/ml.
  • RESULTS: 5.6% (n = 17) of melanoma patients at stage I/II (n = 302) showed increased MIA levels, whereas at stage III/IV (n = 5/n = 19) high levels were found in 60.0% and 89.5% respectively.
  • Patients at stage III/IV with MIA levels below the cut-off turned out to be the ones after metastatic surgery, irradiation or chemotherapy.
  • None of these patients developed further metastases during follow-up, just as patients at stage I/II without increased MIA levels.
  • After a distinct rise of MIA levels, metastases could be detected at the same time or shortly after.
  • On the other hand we saw decreasing levels after or during therapy.
  • CONCLUSION: Our data showed that MIA is a suitable serum marker to detect metastases and to monitor course and therapy of disease.
  • The prognostic value (increased MIA levels at stage I/II), however, requires further investigation.
  • [MeSH-major] Antigens, Tumor-Associated, Carbohydrate / blood. Biomarkers, Tumor / blood. Melanoma / diagnosis
  • [MeSH-minor] Enzyme-Linked Immunosorbent Assay. Female. Follow-Up Studies. Humans. Male. Middle Aged. Neoplasm Metastasis. Neoplasm Staging. Prognosis

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  • (PMID = 11326664.001).
  • [ISSN] 0250-7005
  • [Journal-full-title] Anticancer research
  • [ISO-abbreviation] Anticancer Res.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Greece
  • [Chemical-registry-number] 0 / Antigens, Tumor-Associated, Carbohydrate; 0 / Biomarkers, Tumor; 0 / MIA antigen, human
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41. Luo LM, Huang HF, Pan LY, Shen K, Wu M, Xu L: [Clinical analysis of 42 cases of primary malignant tumor in vagina]. Zhonghua Fu Chan Ke Za Zhi; 2008 Dec;43(12):923-7
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  • [Title] [Clinical analysis of 42 cases of primary malignant tumor in vagina].
  • OBJECTIVE: To analyze the clinical characters, treatment and prognosis of primary malignant tumor in vagina.
  • METHODS: A retrospective analysis of 42 patients diagnosed with primary malignant tumor in vagina in Peking Union Medical College Hospital (PUMCH) between Jan 1984 and Aug 2006 was performed.
  • RESULTS: Primary malignant tumor accounted for 0.98% (42/4286) in the total gynecological malignant tumors during that period in PUMCH.
  • According to the International Federation of Gynecology and Obstetrics (FIGO) staging system, 19 cases were at stage I, 12 cases at stage II, 5 cases at stage III, and 6 cases at stage IV.
  • Thirteen cases were squamous carcinoma, 13 cases were malignant melanoma, 8 cases were adenocarcinoma, 3 cases were yolk sac tumor and 5 cases were other types.
  • The majority of patients were treated with surgery combined with radiotherapy and chemotherapy.
  • The longest follow up was 10 years, with the median time of 2 years.
  • For stage I, stage II and stage III - IV, the 2-year survival rates were 71.3%, 58.3% and 29.6% respectively.
  • The 2-year survival rate of patients with squamous carcinoma was 46.8%, malignant melanoma 72.9%, adenocarcinoma 20.0% and patients with yolk sac tumor were all alive tumor-free after 6 - 10 years' follow up.
  • CONCLUSIONS: The prognosis of primary malignant tumor in vagina is affected by clinical stage and histological type.
  • As to malignant melanoma, radical surgery combined with chemotherapy and immunotherapy produce good effects.
  • Patients with yolk sac tumor can be cured only with chemotherapy.
  • As to other types, more treatment experiences are needed.
  • [MeSH-major] Carcinoma, Squamous Cell / pathology. Carcinoma, Squamous Cell / therapy. Vaginal Neoplasms / pathology. Vaginal Neoplasms / therapy
  • [MeSH-minor] Adolescent. Adult. Aged. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Chemotherapy, Adjuvant. Child. Child, Preschool. Combined Modality Therapy. Female. Follow-Up Studies. Humans. Hysterectomy / methods. Infant. Melanoma / mortality. Melanoma / pathology. Melanoma / surgery. Melanoma / therapy. Middle Aged. Neoplasm Staging. Prognosis. Retrospective Studies. Survival Rate. Vagina / pathology. Vagina / surgery. Young Adult

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  • (PMID = 19134332.001).
  • [ISSN] 0529-567X
  • [Journal-full-title] Zhonghua fu chan ke za zhi
  • [ISO-abbreviation] Zhonghua Fu Chan Ke Za Zhi
  • [Language] chi
  • [Publication-type] English Abstract; Journal Article
  • [Publication-country] China
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42. An JS, Wu LY, Li N, Li B, Yu GZ, Liu LY: [Clinical analysis of 42 cases of primary malignant melanoma in female genital tract]. Zhonghua Fu Chan Ke Za Zhi; 2007 May;42(5):320-4
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  • [Title] [Clinical analysis of 42 cases of primary malignant melanoma in female genital tract].
  • OBJECTIVE: To analyze the clinical characteristics, diagnosis, treatment and prognosis of primary malignant melanoma in female genital tract.
  • METHODS: The clinical data of 42 patients of primary malignant melanoma in female genital tract were reviewed.
  • S-100 protein was positive in all cases, and monoclonal antibody to melanoma of human (HMB-45) was positive in 14 cases.
  • The 2-year cumulative overall survival rates for the patients of early stage [International Federation of Gynecology and Obstetrics (FIGO) stage I and II] and that of advanced stage (stage III and IV) were 77% and 34% respectively (P < 0.05).
  • The 2-year cumulative overall survival rates for the patients of stage I and stage II were 78% and 74% respectively (P = 0.303).
  • In the 40 patients who received surgery, univariate analysis showed that the adjuvant chemotherapy improved the recurrence-free survival and the overall survival significantly (P < 0.05), and the other factors including radical surgery, regional lymphadenectomy, biotherapy and radiotherapy did not affect prognosis (P > 0.05).
  • Compared with chemotherapy, biochemotherapy did not improve prognosis significantly (P > 0.05).
  • CONCLUSIONS: Biopsy for the malignant melanoma in female genital tract has high misdiagnosis rate.
  • Immunohistochemistry assay could improve diagnosis markedly.
  • The FIGO staging system fails to predict the prognosis accurately.
  • Surgery plays an important role in treatment, while the adjuvant chemotherapy could improve survival effectively.
  • [MeSH-major] Genital Neoplasms, Female / diagnosis. Genital Neoplasms, Female / therapy. Melanoma / diagnosis. Melanoma / therapy
  • [MeSH-minor] Adolescent. Adult. Aged. Aged, 80 and over. Antigens, Neoplasm / analysis. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Chemotherapy, Adjuvant. Combined Modality Therapy. Disease-Free Survival. Female. Humans. Immunohistochemistry. Lymph Node Excision. Melanoma-Specific Antigens. Middle Aged. Neoplasm Proteins / analysis. Neoplasm Staging. Prognosis. Radiotherapy. Retrospective Studies. S100 Proteins / analysis. Uterine Cervical Neoplasms / diagnosis. Uterine Cervical Neoplasms / metabolism. Uterine Cervical Neoplasms / therapy. Vaginal Neoplasms / diagnosis. Vaginal Neoplasms / metabolism. Vaginal Neoplasms / therapy. Vulvar Neoplasms / diagnosis. Vulvar Neoplasms / metabolism. Vulvar Neoplasms / therapy

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  • (PMID = 17673044.001).
  • [ISSN] 0529-567X
  • [Journal-full-title] Zhonghua fu chan ke za zhi
  • [ISO-abbreviation] Zhonghua Fu Chan Ke Za Zhi
  • [Language] chi
  • [Publication-type] English Abstract; Journal Article
  • [Publication-country] China
  • [Chemical-registry-number] 0 / Antigens, Neoplasm; 0 / Melanoma-Specific Antigens; 0 / Neoplasm Proteins; 0 / S100 Proteins
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43. Juergensen A, Holzapfel U, Hein R, Stolz W, Buettner R, Bosserhoff A: Comparison of two prognostic markers for malignant melanoma: MIA and S100 beta. Tumour Biol; 2001 Jan-Feb;22(1):54-8
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  • [Title] Comparison of two prognostic markers for malignant melanoma: MIA and S100 beta.
  • It has recently been shown that the serum level of melanoma-inhibitory protein (MIA) provides useful information for the therapy and follow-up of patients with malignant melanoma.
  • Previously, S100 beta has been described as a useful tumor marker for malignant melanoma.
  • In this study, we compare the significance of the two markers in follow-up, therapy outcome and prognosis by measuring MIA and S100 beta serum levels in 50 melanoma patients.
  • Serum levels were measured in patients with malignant melanomas of stages I-IV with at least 3 time points of measurement.
  • Serial MIA and S100 beta measurements were obtained from 32 patients with stage IV disease in parallel to chemotherapy and from 18 patients with a history of stage I and stage II disease during follow-up.
  • The response to chemotherapy in stage IV disease and relapse of melanoma during follow-up correlated with changes in MIA and S100 beta serum levels.
  • In conclusion, both markers are useful for detection of progression from localized to metastatic disease during follow-up and for monitoring therapy of advanced melanomas.
  • [MeSH-major] Biomarkers, Tumor / blood. Melanoma / blood. Neoplasm Proteins / blood. S100 Proteins / blood. Skin Neoplasms / blood
  • [MeSH-minor] Adult. Aged. Combined Modality Therapy. Disease Progression. Enzyme-Linked Immunosorbent Assay. Evaluation Studies as Topic. Extracellular Matrix Proteins. Female. Follow-Up Studies. Humans. Life Tables. Luminescent Measurements. Male. Middle Aged. Prognosis. Sensitivity and Specificity. Survival Analysis

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  • [Copyright] Copyright 2000 S. Karger AG, Basel.
  • (PMID = 11054027.001).
  • [ISSN] 1010-4283
  • [Journal-full-title] Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine
  • [ISO-abbreviation] Tumour Biol.
  • [Language] eng
  • [Publication-type] Comparative Study; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Biomarkers, Tumor; 0 / Extracellular Matrix Proteins; 0 / MIA protein, human; 0 / Neoplasm Proteins; 0 / S100 Proteins; 0 / S100A1 protein
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44. Helfrich I, Scheffrahn I, Bartling S, Weis J, von Felbert V, Middleton M, Kato M, Ergün S, Augustin HG, Schadendorf D: Resistance to antiangiogenic therapy is directed by vascular phenotype, vessel stabilization, and maturation in malignant melanoma. J Exp Med; 2010 Mar 15;207(3):491-503
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  • [Title] Resistance to antiangiogenic therapy is directed by vascular phenotype, vessel stabilization, and maturation in malignant melanoma.
  • We hypothesized that the level of vessel maturation is critically involved in the response to antiangiogenic therapies.
  • To test this hypothesis, we evaluated the vascular network in spontaneously developing melanomas of MT/ret transgenic mice after using PTK787/ZK222584 for anti-VEGF therapy but also analyzed human melanoma metastases taken at clinical relapse in patients undergoing adjuvant treatment using bevacizumab.
  • Both experimental settings showed that tumor vessels, which are resistant to anti-VEGF therapy, are characterized by enhanced vessel diameter and normalization of the vascular bed by coverage of mature pericytes and immunoreactivity for desmin, NG-2, platelet-derived growth factor receptor beta, and the late-stage maturity marker alpha smooth muscle actin.
  • Our findings emphasize that the level of mural cell differentiation and stabilization of the vascular wall significantly contribute to the response toward antiangiogenic therapy in melanoma.
  • This study may be useful in paving the way toward a more rational development of second generation antiangiogenic combination therapies and in providing, for the first time, a murine model to study this.
  • [MeSH-major] Angiogenesis Inhibitors / therapeutic use. Drug Resistance, Neoplasm. Melanoma / drug therapy. Melanoma / genetics

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  • (PMID = 20194633.001).
  • [ISSN] 1540-9538
  • [Journal-full-title] The Journal of experimental medicine
  • [ISO-abbreviation] J. Exp. Med.
  • [Language] eng
  • [Grant] United Kingdom / Cancer Research UK / / 8466
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Angiogenesis Inhibitors; 0 / Desmin; 0 / Vascular Endothelial Growth Factor A; EC 2.7.10.1 / Receptor, Platelet-Derived Growth Factor beta
  • [Other-IDs] NLM/ PMC2839146
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45. Singer M, Mutch MG: Anal melanoma. Clin Colon Rectal Surg; 2006 May;19(2):78-87
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  • [Title] Anal melanoma.
  • Anal melanoma is rare and aggressive malignancy.
  • Unlike cutaneous melanoma, anal melanoma has no known risk factors.
  • Surgical excision remains the cornerstone of therapy.
  • There are no long-term survivors of stage II or III disease; therefore, early diagnosis and treatment remain crucial.
  • Adjuvant chemotherapy, interferon, and radiation may offer some benefit.

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  • (PMID = 20011314.001).
  • [ISSN] 1530-9681
  • [Journal-full-title] Clinics in colon and rectal surgery
  • [ISO-abbreviation] Clin Colon Rectal Surg
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Other-IDs] NLM/ PMC2780102
  • [Keywords] NOTNLM ; Melanoma / abdominoperineal resection / anal / malignancy / wide local excision
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46. Fujita M, High WA, Asgari S, Lewis KD, Gonzalez R: Development of vitiligo during melanoma treatment with a novel survivin inhibitor: a case report and review of the literature. Int J Dermatol; 2009 Apr;48(4):426-30
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  • [Title] Development of vitiligo during melanoma treatment with a novel survivin inhibitor: a case report and review of the literature.
  • BACKGROUND: The development of vitiligo has been associated with an improved clinical response in melanoma patients.
  • METHODS: We report a case of vitiligo associated with a novel antisurvivin drug and review the literature to determine the pathogenesis of vitiligo occurring during melanoma treatment.
  • RESULTS: A 78-year-old man with stage IV malignant melanoma developed vitiligo after the first therapeutic cycle of a novel antisurvivin drug.
  • Although his vitiligo remained static, his melanoma continued to progress and he died in 8 months.
  • A review of the literature demonstrates a relationship between vitiligo development and improved clinical response in many melanoma cases treated with immunotherapy; however, the relationship may depend on the type of treatment.
  • CONCLUSIONS: Understanding complex immune responses in vitiliginous skin and melanoma sites is important in order to interpret the development of vitiligo occurring during melanoma treatment.
  • [MeSH-major] Antineoplastic Agents / adverse effects. Imidazoles / adverse effects. Melanoma / drug therapy. Microtubule-Associated Proteins / antagonists & inhibitors. Naphthoquinones / adverse effects. Skin Neoplasms / drug therapy. Vitiligo / chemically induced

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  • (PMID = 19335434.001).
  • [ISSN] 1365-4632
  • [Journal-full-title] International journal of dermatology
  • [ISO-abbreviation] Int. J. Dermatol.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / BIRC5 protein, human; 0 / Imidazoles; 0 / Inhibitor of Apoptosis Proteins; 0 / Microtubule-Associated Proteins; 0 / Naphthoquinones; 0 / YM 155
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47. Ribas A: Overcoming immunologic tolerance to melanoma: targeting CTLA-4 with tremelimumab (CP-675,206). Oncologist; 2008;13 Suppl 4:10-5
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  • [Title] Overcoming immunologic tolerance to melanoma: targeting CTLA-4 with tremelimumab (CP-675,206).
  • Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) blockade therapies have been evaluated in clinical trials and have shown promise as possible options for treating patients with cancer.
  • One agent under investigation is tremelimumab (CP-675,206), a monoclonal antibody that has been demonstrated to be a safe and efficacious treatment in patients with malignant melanoma.
  • A pivotal phase II clinical trial assessing single-agent tremelimumab as second-line therapy in metastatic melanoma has completed accrual, with response rate as the primary endpoint.
  • [MeSH-major] Antibodies, Monoclonal / therapeutic use. Antigens, CD / immunology. Immunotherapy. Melanoma / drug therapy

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  • (PMID = 19001146.001).
  • [ISSN] 1549-490X
  • [Journal-full-title] The oncologist
  • [ISO-abbreviation] Oncologist
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Antigens, CD; 0 / CTLA-4 Antigen; 0 / CTLA4 protein, human; QEN1X95CIX / tremelimumab
  • [Number-of-references] 10
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48. Engell-Noerregaard L, Hansen TH, Andersen MH, Thor Straten P, Svane IM: Review of clinical studies on dendritic cell-based vaccination of patients with malignant melanoma: assessment of correlation between clinical response and vaccine parameters. Cancer Immunol Immunother; 2009 Jan;58(1):1-14
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  • [Title] Review of clinical studies on dendritic cell-based vaccination of patients with malignant melanoma: assessment of correlation between clinical response and vaccine parameters.
  • During the past years numerous clinical trials have been carried out to assess the ability of dendritic cell (DC) based immunotherapy to induce clinically relevant immune responses in patients with malignant diseases.
  • A broad range of cancer types have been targeted including malignant melanoma which in the disseminated stage have a very poor prognosis and only limited treatment options with moderate effectiveness.
  • Herein we describe the results of a focused search of recently published clinical studies on dendritic cell vaccination in melanoma and review different vaccine parameters which are frequently claimed to have a possible influence on clinical response.
  • These parameters include performance status, type of antigen, DC maturation status, route of vaccine administration, use of adjuvant, and vaccine induced immune response.
  • In total, 38 articles found through Medline search, have been included for analysis covering a total of 626 patients with malignant melanoma treated with DC based therapy.
  • Clinical response (CR, PR and SD) were found to be significantly correlated with the use of peptide antigens (p = 0.03), the use of any helper antigen/adjuvant (p = 0.002), and induction of antigen specific T cells (p = 0.0004).
  • No significant correlations between objective response (CR and PR) and the tested parameters were found.
  • However, a few non-significant trends were demonstrated; these included an association between objective response and use of immature DCs (p = 0.08), use of adjuvant (p = 0.09), and use of autologous antigen preparation (p = 0.12).
  • Important lessons can be learned from previous studies, interpretation of these findings should, however, be done with reservation for the many minor deviations in the different treatment schedules among the published studies, which were not considered in order to be able to process and group the data.
  • [MeSH-major] Cancer Vaccines. Dendritic Cells / immunology. Melanoma / drug therapy

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  • (PMID = 18719915.001).
  • [ISSN] 1432-0851
  • [Journal-full-title] Cancer immunology, immunotherapy : CII
  • [ISO-abbreviation] Cancer Immunol. Immunother.
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / Cancer Vaccines
  • [Number-of-references] 80
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49. Doerler M, Hyun J, Venten I, Potthoff A, Bartke U, Serova K, Hoextermann S, Altmeyer P, Brockmeyer NH: Does chemosensitivity-assay-directed therapy have an influence on the prognosis of patients with malignant melanoma stage IV? A retrospective study of 14 patients with malignant melanoma stage IV. Eur J Med Res; 2007 Oct 30;12(10):497-502
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Does chemosensitivity-assay-directed therapy have an influence on the prognosis of patients with malignant melanoma stage IV? A retrospective study of 14 patients with malignant melanoma stage IV.
  • OBJECTIVE: To evaluate the efficacy of chemosensitivity-testing directed chemotherapy in comparison with empirically chosen therapy regimens in patients with malignant melanoma stage IV.
  • PATIENTS AND METHODS: Retrospective study including 14 patients with histologically confirmed malignant melanoma and diagnosis of stage IV disease by routine diagnostic procedures.
  • Patients in group A (n = 7) were treated according to their individual chemosensitivity testing results, whereas patients in group B (n = 7) received empirically chosen treatment regimens.
  • The log-rank test was performed to compare the overall survival according to treatment group, LDH level in serum and AJCC-category.
  • To compare the distribution of sex, LDH level in serum and AJCC-category between the treatment groups, the Fisher exact test was used.
  • LDH level in serum at study entry showed a strong correlation with overall survival, with normal LDH levels leading to a statistically significant longer survival (p = 0.006 for the log-rank test, respectively).
  • Moreover, stage AJCC M1a/b yielded to a better prognosis compared with stage AJCC M1c (log-rank test p = 0.066; not statistically significant).
  • CONCLUSION: Chemosensitivity-assay directed therapy might be a useful tool in determining the optimized chemotherapeutic drug or drug combination in the individual patient and might contribute to a better prognosis in patients with metastatic melanoma stage IV.
  • [MeSH-major] Drug Therapy. Melanoma
  • [MeSH-minor] Adult. Aged. Female. Humans. Male. Middle Aged. Neoplasm Staging. Prognosis. Proportional Hazards Models. Retrospective Studies. Survival Analysis. Treatment Outcome

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  • (PMID = 18024256.001).
  • [ISSN] 0949-2321
  • [Journal-full-title] European journal of medical research
  • [ISO-abbreviation] Eur. J. Med. Res.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Germany
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50. Nashan D, Müller ML, Grabbe S, Wustlich S, Enk A: Systemic therapy of disseminated malignant melanoma: an evidence-based overview of the state-of-the-art in daily routine. J Eur Acad Dermatol Venereol; 2007 Nov;21(10):1305-18
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Systemic therapy of disseminated malignant melanoma: an evidence-based overview of the state-of-the-art in daily routine.
  • AIMS: In the metastatic stage, malignant melanoma is resistant to systemic treatment and carries a poor prognosis.
  • MATERIAL AND METHODS: A critical, evidence-based analysis of standard approaches and their variations to systemic therapy based on an extended search of published literature and from different Internet sources is presented.
  • Therefore, assessment of therapies is mainly based on randomized multicentre studies or clinical studies achieving an evidence level grade 1 or 2.
  • Combination of polychemotherapy with the cytokines interferon-alpha and interleukin-2 substantially augments chemotherapy induced response rates, but a meta-analysis for survival does not support its therapeutic superiority.
  • Biological therapies such as vaccinations have not yet delivered results on a higher evidence level.
  • CONCLUSIONS: Although the therapeutic efficacy is very limited, dacarbazine cannot be rejected as standard therapy for disseminated melanoma, because no other therapeutic regimen exhibits a survival benefit over DTIC in an evidence-based analysis.
  • This lack of therapeutic progress over the past 40 years clearly calls for further clinical studies, and patients should be enrolled into clinical trials whenever possible.
  • [MeSH-major] Antineoplastic Agents, Alkylating / therapeutic use. Dacarbazine / therapeutic use. Melanoma / drug therapy
  • [MeSH-minor] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Cancer Vaccines. Evidence-Based Medicine. Humans. Immunotherapy. Interferon-alpha / therapeutic use. Interleukin-2 / therapeutic use. Neoplasm Metastasis. Prognosis

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  • (PMID = 17958834.001).
  • [ISSN] 0926-9959
  • [Journal-full-title] Journal of the European Academy of Dermatology and Venereology : JEADV
  • [ISO-abbreviation] J Eur Acad Dermatol Venereol
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] Netherlands
  • [Chemical-registry-number] 0 / Antineoplastic Agents, Alkylating; 0 / Cancer Vaccines; 0 / Interferon-alpha; 0 / Interleukin-2; 7GR28W0FJI / Dacarbazine
  • [Number-of-references] 173
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51. Mitchell MS, Abrams J, Thompson JA, Kashani-Sabet M, DeConti RC, Hwu WJ, Atkins MB, Whitman E, Ernstoff MS, Haluska FG, Jakowatz JG, Das Gupta TK, Richards JM, Samlowski WE, Costanzi JJ, Aronson FR, Deisseroth AB, Dudek AZ, Jones VE: Randomized trial of an allogeneic melanoma lysate vaccine with low-dose interferon Alfa-2b compared with high-dose interferon Alfa-2b for Resected stage III cutaneous melanoma. J Clin Oncol; 2007 May 20;25(15):2078-85
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  • [Title] Randomized trial of an allogeneic melanoma lysate vaccine with low-dose interferon Alfa-2b compared with high-dose interferon Alfa-2b for Resected stage III cutaneous melanoma.
  • PURPOSE: To compare the overall survival (OS) of patients with resected stage III melanoma administered active specific immunotherapy and low-dose interferon alfa-2b (IFN-alpha-2b) with the OS achieved using high-dose IFN-alpha-2b.
  • PATIENTS AND METHODS: An Ad Hoc Melanoma Working Group of 25 investigators treated 604 patients from April 1997 to January 2003.
  • Patients were stratified by sex and number of nodes and were randomly assigned to receive either 2 years of treatment with active specific immunotherapy with allogeneic melanoma lysates and low-dose IFN-alpha-2b (arm 1) or high-dose IFN-alpha-2b alone for 1 year (arm 2).
  • RESULTS: Median follow-up time was 32 months for all patients and 42 months for surviving patients.
  • Median OS time exceeds 84 months in arm 1 and is 83 months in arm 2 (P = .56).
  • Estimated 5-year relapse-free survival (RFS) rate is 50% in arm 1 and 48% in arm 2, with median RFS times of 58 and 50 months, respectively.
  • The incidence of serious adverse events as a result of treatment was the same in both arms, but more severe neuropsychiatric toxicity was seen in arm 2.
  • Long RFS and OS times were observed in both treatment arms.
  • [MeSH-major] Cancer Vaccines / therapeutic use. Immunotherapy, Active. Interferon-alpha / therapeutic use. Melanoma / therapy. Skin Neoplasms / therapy
  • [MeSH-minor] Combined Modality Therapy. Cytoskeletal Proteins. Dose-Response Relationship, Drug. Drug Combinations. Female. Follow-Up Studies. Humans. Lipid A / analogs & derivatives. Lymphatic Metastasis. Male. Middle Aged. Neoplasm Recurrence, Local. Recombinant Proteins. Survival Rate

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  • [CommentIn] Expert Rev Vaccines. 2007 Dec;6(6):907-11 [18377354.001]
  • [CommentIn] J Clin Oncol. 2007 Oct 10;25(29):4693; author reply 4693-5 [17925569.001]
  • (PMID = 17513813.001).
  • [ISSN] 1527-7755
  • [Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • [ISO-abbreviation] J. Clin. Oncol.
  • [Language] eng
  • [Publication-type] Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Cancer Vaccines; 0 / Cytoskeletal Proteins; 0 / Drug Combinations; 0 / Interferon-alpha; 0 / Lipid A; 0 / Melacine; 0 / Recombinant Proteins; 0 / detox adjuvant; 99210-65-8 / interferon alfa-2b
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52. Peng RQ, Wu GH, Chen WK, Ding Y, Ma J, Zhang NH, Su YS, Zhang XS: [Clinical characteristics and prognosis of primary nasal mucosal melanoma--a report of 44 cases]. Ai Zheng; 2006 Oct;25(10):1284-6
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  • [Title] [Clinical characteristics and prognosis of primary nasal mucosal melanoma--a report of 44 cases].
  • BACKGROUND & OBJECTIVE: Primary mucosal malignant melanoma of the nasal cavity, paranasal sinuses, and nasopharynx is rare and current research data of this disease are mainly from western populations.
  • 2005, 66 patients with primary nasal mucosal melanoma were treated in Cancer Center of Sun Yat-sen University, China.
  • Demographics and baseline characteristics, treatments, recurrence, metastasis, and survival were documented in hospital records.
  • Of the 31 patients received operation-dominated treatment, 8 received adjuvant radiotherapy, 13 received adjuvant chemotherapy, and 6 received adjuvant non-specific immunotherapy.
  • The median time of follow-up was 29 months.
  • The median survival time was 24 months and the 5-year survival time was 25%.
  • Clinical stage affected prognosis, whereas age, gender, site, primary tumor mass, and adjuvant therapy were not correlated to survival status.
  • CONCLUSION: Nasal mucosal melanoma has high incidence of local recurrence and distant metastasis, especially cervical lymphadenopathy.
  • Clinical stage affects the prognosis.
  • [MeSH-major] Melanoma. Nasal Mucosa. Neoplasm Recurrence, Local. Nose Neoplasms
  • [MeSH-minor] Adolescent. Adult. Aged. Chemotherapy, Adjuvant. Child. Child, Preschool. Female. Follow-Up Studies. Humans. Infant. Lung Neoplasms / secondary. Lymphatic Metastasis. Male. Middle Aged. Nasal Cavity. Neoplasm Staging. Paranasal Sinus Neoplasms / pathology. Paranasal Sinus Neoplasms / surgery. Paranasal Sinus Neoplasms / therapy. Radiotherapy, Adjuvant. Retrospective Studies. Survival Rate

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  • (PMID = 17059777.001).
  • [Journal-full-title] Ai zheng = Aizheng = Chinese journal of cancer
  • [ISO-abbreviation] Ai Zheng
  • [Language] chi
  • [Publication-type] English Abstract; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] China
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53. Liu YS, Zhang WD, Yang CH, Sun YF, Geng B: [Effect of interferon alfa therapy on malignant melanoma of oral mucosa]. Shanghai Kou Qiang Yi Xue; 2006 Jun;15(3):263-8
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  • [Title] [Effect of interferon alfa therapy on malignant melanoma of oral mucosa].
  • PURPOSE: To evaluate the effect of two adjuvant therapy in patients with resected maxillary mucosal melanoma.
  • There were 165 patients with resected maxillary mucosal malignant melanoma in the study, which were divided into three group: control group (50), interferon-alpha2b group (78) and interferon-alpha2b+dacarbazine group (37).
  • All patients had stage II or III lesions according to AJCC(2000) staying system.
  • Kaplan-Meire method was used to calculate the cumulated survival rate with 3 different treatments and Log-rank method for comparison of the distribution of the different survival rates in 3 groups.
  • The significant prognostic factors included thickness(P<0.001, RR=2.696), ulceration(P<0.001, RR=2.068), lymph node metastasis(P<0.001, RR=1.710) and the treatment method(P<0.001, RR=0.395).
  • CONCLUSIONS: The two conjunctive methods used in this study can improve the overall survival in patients with resected maxillary mucosal melanoma.
  • [MeSH-major] Dacarbazine / therapeutic use. Interferon-alpha / therapeutic use. Melanoma / drug therapy. Mouth Mucosa / pathology. Mouth Neoplasms / pathology
  • [MeSH-minor] Antineoplastic Agents / therapeutic use. Humans. Lymphatic Metastasis. Maxilla. Recombinant Proteins / therapeutic use. Retrospective Studies. Survival Rate

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  • (PMID = 16862358.001).
  • [ISSN] 1006-7248
  • [Journal-full-title] Shanghai kou qiang yi xue = Shanghai journal of stomatology
  • [ISO-abbreviation] Shanghai Kou Qiang Yi Xue
  • [Language] chi
  • [Publication-type] Comparative Study; English Abstract; Journal Article
  • [Publication-country] China
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Interferon-alpha; 0 / Recombinant Proteins; 7GR28W0FJI / Dacarbazine; 99210-65-8 / interferon alfa-2b
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54. Richtig E, Langmann G, Schlemmer G, Müllner K, Papaefthymiou G, Bergthaler P, Smolle J: [Safety and efficacy of interferon alfa-2b in the adjuvant treatment of uveal melanoma]. Ophthalmologe; 2006 Jun;103(6):506-11
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  • [Title] [Safety and efficacy of interferon alfa-2b in the adjuvant treatment of uveal melanoma].
  • PURPOSE: In this manuscript, the safety and efficacy of adjuvant interferon alfa 2b treatment of uveal melanoma is described.
  • PATIENTS AND METHODS: A total of 39 patients (23 male and 16 female, mean age 56.5 years, range 35-78 years) with uveal melanoma were treated with interferon alfa 2b, 3 million units three times a week subcutaneously for 1 year after therapy of the primary tumor.
  • In all patients age, gender, primary melanoma data, therapeutic interventions, treatment side effects and outcome were documented.
  • RESULTS: Of the 39 patients, 31 (80%) finished the treatment as scheduled after 1 year.
  • In eight patients, therapy had to be withdrawn because of serious side effects (five patients) and the appearance of metastases (three patients).
  • Neither a univariate approach nor a multivariate approach could show a protective effect of interferon treatment on survival.
  • CONCLUSIONS: Adjuvant treatment of uveal melanoma with interferon alfa should be abandoned until the question of dose and administration for cutaneous melanoma is solved.
  • [MeSH-major] Interferon-alpha / administration & dosage. Interferon-alpha / adverse effects. Melanoma / drug therapy. Risk Assessment / methods. Uveal Neoplasms / drug therapy
  • [MeSH-minor] Adult. Aged. Antineoplastic Agents / administration & dosage. Antineoplastic Agents / adverse effects. Chemotherapy, Adjuvant. Female. Humans. Male. Middle Aged. Recombinant Proteins. Risk Factors. Treatment Outcome

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  • (PMID = 16763868.001).
  • [ISSN] 0941-293X
  • [Journal-full-title] Der Ophthalmologe : Zeitschrift der Deutschen Ophthalmologischen Gesellschaft
  • [ISO-abbreviation] Ophthalmologe
  • [Language] ger
  • [Publication-type] Clinical Trial; Journal Article
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Interferon-alpha; 0 / Recombinant Proteins; 43K1W2T1M6 / interferon alfa-2b
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55. Lewis KD, Gibbs P, O'Day S, Richards J, Weber J, Anderson C, Zeng C, Baron A, Russ P, Gonzalez R: A phase II study of biochemotherapy for advanced melanoma incorporating temozolomide, decrescendo interleukin-2 and GM-CSF. Cancer Invest; 2005;23(4):303-8
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] A phase II study of biochemotherapy for advanced melanoma incorporating temozolomide, decrescendo interleukin-2 and GM-CSF.
  • Metastatic malignant melanoma remains a very difficult disease to treat.
  • Previous phase II studies using biochemotherapy (combination of platinum-containing chemotherapy with IL-2 and IFNalpha) have shown response rates of about 50%.
  • However, a site of frequent relapse is in the central nervous system (CNS).
  • We report the results of a phase II study using a novel biochemotherapy regimen containing temozolomide, cisplatin, decrescendo IL-2, IFNalpha, and GM-CSF in the treatment of stage IV melanoma.
  • Seventy-one patients with histologically confirmed metastatic melanoma were enrolled between June 1998 and October 1999.
  • Prior chemotherapy or IL-2 was not permitted.
  • Patients received temozolomide 150 mg/m2 orally days 1-5, cisplatin 30 mg/m2 IV days 1-3, IFNalpha 5 MU/m2 SQ on days 1-5, and IL-2 was administered in a decrescendo fashion according to the following schedule: day 1: 18 MU/m2 continuous IV infusion over 6 hours; day 2: 18 MU/m2 continuous IV infusion over 12 hours; day 3: 9 MU/m2 subcutaneously q12 hours; day 4: 4.5 MU/m2 subcutaneously x 1.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Melanoma / drug therapy
  • [MeSH-minor] Adult. Aged. Antineoplastic Agents, Alkylating / administration & dosage. Brain Neoplasms / mortality. Brain Neoplasms / secondary. Dacarbazine / administration & dosage. Dacarbazine / analogs & derivatives. Eye Neoplasms / drug therapy. Eye Neoplasms / mortality. Eye Neoplasms / pathology. Granulocyte-Macrophage Colony-Stimulating Factor / administration & dosage. Humans. Interleukin-2 / administration & dosage. Middle Aged. Neoplasm Metastasis. Reproducibility of Results. Skin Neoplasms / drug therapy. Skin Neoplasms / mortality. Skin Neoplasms / pathology. Survival Analysis

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  • (PMID = 16100942.001).
  • [ISSN] 0735-7907
  • [Journal-full-title] Cancer investigation
  • [ISO-abbreviation] Cancer Invest.
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / P30 CA46934
  • [Publication-type] Clinical Trial; Clinical Trial, Phase II; Journal Article; Multicenter Study; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, P.H.S.
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents, Alkylating; 0 / Interleukin-2; 7GR28W0FJI / Dacarbazine; 83869-56-1 / Granulocyte-Macrophage Colony-Stimulating Factor; 85622-93-1 / temozolomide
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56. Jahnke A, Makovitzky J, Briese V: Primary melanoma of the female genital system: a report of 10 cases and review of the literature. Anticancer Res; 2005 May-Jun;25(3A):1567-74
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  • [Title] Primary melanoma of the female genital system: a report of 10 cases and review of the literature.
  • BACKGROUND: Primary melanoma of the female genital system are extremely rare (2-3%).
  • PATIENTS AND METHODS: A retrospective review was undertaken of patients with primary melanoma of the female genital system treated from 1990-2003 at Rostock University Hospital, Germany.
  • Different treatments (sentinel node biopsy, inguinofemoral lymphadenectomy, en bloc resection, adjuvant Interferon-alpha-therapy, adjuvant chemotherapy) are discussed.
  • The complicated classification is reduced to a clinical path for daily use (UICC stage and invasion depth of Breslow, Clark's level and Chung's level).
  • RESULTS: We report on 10 patients, aged 26 to 76 years, with primary melanoma of the female genital tract.
  • Seven women developed a vulvar melanoma and one woman a malignant melanoma of the cutaneous inguinal region, while another 2 women had an unusual primary location of the malignant melanoma, the cervico-vaginal region (n=1) and the left ovary (n = 1).
  • [MeSH-major] Genital Neoplasms, Female / diagnosis. Melanoma / diagnosis
  • [MeSH-minor] Adult. Aged. Chemotherapy, Adjuvant. Combined Modality Therapy. Female. Humans. Interferon-alpha / therapeutic use. Lymph Node Excision. Middle Aged. Retrospective Studies

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  • (PMID = 16033062.001).
  • [ISSN] 0250-7005
  • [Journal-full-title] Anticancer research
  • [ISO-abbreviation] Anticancer Res.
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] Greece
  • [Chemical-registry-number] 0 / Interferon-alpha
  • [Number-of-references] 27
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57. Tímár J, Nemzeti Onkológiai Kutatás-fejlesztési Konzorcium: [Activity of the National Oncology R&D Consortium in 2004]. Magy Onkol; 2005;49(1):3-7
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  • We have prepared the map of regional distribution of cervical cancer in Hungary.
  • A cost-effective molecular staging method was introduced to the management of breast cancer patients.
  • Genomic profiling identified the gene signature of Herceptin and taxane sensitivity of breast cancer.
  • In colon cancer patients we have determined the mutational spectrum of hMLH1 and hMSH2 genes in Hungary.
  • The prognostic power of SHMT and MTHFR polymorphism was determined in colorectal cancer patients.
  • In head and neck cancer the gene signature of cisplatin sensitivity and the EGFR polymorphism was determined.
  • We have introduced a cost-effective in vitro assay to determine the drug resistance of pediatric leukemias.
  • The prognostic power of N-myc genotyping was determined in neuroblastoma patients.
  • A phase I trial for gene therapy of brain cancer was started by using a GM-CSF adenoviral vector system.
  • Using global genomic approaches the gene signature of malignant melanoma and its metastatic disease was determined.
  • We have found that Ca-channel blockers and EGFR tyrosine kinase inhibitors are effective in preclinical human melanoma models in breaking the apoptosis resistance of this tumor.
  • [MeSH-minor] Breast Neoplasms / diagnosis. Breast Neoplasms / epidemiology. Breast Neoplasms / genetics. Breast Neoplasms / therapy. Colonic Neoplasms / diagnosis. Colonic Neoplasms / epidemiology. Colonic Neoplasms / genetics. Colonic Neoplasms / therapy. Disease Progression. Female. Government Agencies. Head and Neck Neoplasms / diagnosis. Head and Neck Neoplasms / epidemiology. Head and Neck Neoplasms / genetics. Head and Neck Neoplasms / therapy. Humans. Hungary. Journalism, Medical. Male

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  • (PMID = 15902326.001).
  • [ISSN] 0025-0244
  • [Journal-full-title] Magyar onkologia
  • [ISO-abbreviation] Magy Onkol
  • [Language] hun
  • [Publication-type] English Abstract; Journal Article; Research Support, Non-U.S. Gov't; Review
  • [Publication-country] Hungary
  • [Number-of-references] 32
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58. Crott R: Cost effectiveness and cost utility of adjuvant interferon alpha in cutaneous melanoma: a review. Pharmacoeconomics; 2004;22(9):569-80
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  • [Title] Cost effectiveness and cost utility of adjuvant interferon alpha in cutaneous melanoma: a review.
  • Although interferon alpha (IFN) has been approved since 1995 in the US as adjuvant therapy for high-risk melanoma patients, its cost effectiveness and economic value have only been recently addressed.
  • There are very few papers that address the overall cost and cost components of treating melanoma patients, all of them focusing on the US.
  • These studies showed the large cost of treatment of stage III and IV patients (around $US40,000-60,000 [1997/8 values]).
  • Chemotherapy and adjuvant immunomodulators comprised a large part of this cost.
  • Cost-effectiveness studies performed for the US, Spain and Italy have been largely based on the results of the pivotal Eastern Cooperative Oncology Group (ECOG) 1684 trial using high-dose (10-20 Megaunits [MU]/m(2)) IFN in mainly stage III patients.
  • Incremental cost-effectiveness ratios for adjuvant IFN versus observation from these studies fall in the range of $US13,000-40,000 per life-year gained (1998 values), depending on the time horizon, discount rate and cost of IFN, with an extrapolated life-gain over lifetime ranging between 1.9 and 3 years.
  • Only one study, the French Cooperative Melanoma Group trial in stage IIA/B patients, used low-dose (3 MU(2)) IFN and yielded a quite favourable incremental cost effectiveness ratio (cost per life-year gained) ranging from $US12,954 over 5 years (survival gain 3 months) to $US1,544 over a lifetime (extrapolated survival gain 2.6 years) [1995 values].
  • Although these results could be seen as supporting the more widespread use of adjuvant IFN in melanoma, it should be stressed that they were based on the only two positive clinical trials out of a total of ten.
  • The eight negative high-dose (HDI) and low-dose (LDI) IFN trials have failed to show an impact on survival (HDI: ECOG 1690 and North Central Cancer Treatment Group [NCCTG]; LDI: ECOG 1690, WHO-16, UK Coordinating Committee on Cancer Research [UKCCRC] and Austrian, Scottish and European Organisation for Research and Treatment of Cancer trials).
  • A definitive appraisal of the cost effectiveness of IFN in melanoma patients will have to await these results and their economic analyses.
  • [MeSH-major] Adjuvants, Immunologic / economics. Interferon-alpha / economics. Melanoma / economics. Skin Neoplasms / economics
  • [MeSH-minor] Chemotherapy, Adjuvant. Clinical Trials as Topic. Cost-Benefit Analysis. Health Care Costs. Humans. Neoplasm Staging. Quality of Life. Survival Analysis

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  • (PMID = 15209526.001).
  • [ISSN] 1170-7690
  • [Journal-full-title] PharmacoEconomics
  • [ISO-abbreviation] Pharmacoeconomics
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] New Zealand
  • [Chemical-registry-number] 0 / Adjuvants, Immunologic; 0 / Interferon-alpha
  • [Number-of-references] 38
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59. Wysocki PJ, Karczewska A, Mackiewicz A: [Gene modified tumor vaccines in therapy of malignant melanoma]. Otolaryngol Pol; 2002;56(2):147-53
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  • [Title] [Gene modified tumor vaccines in therapy of malignant melanoma].
  • Over the years the incidence of malignant melanoma in Poland as well as in other countries has been continuously increasing.
  • Surgery is a treatment of choice in the early stages of primary lesions.
  • Advanced malignant melanoma however is resistant to chemotherapy or radiotherapy.
  • Therefore there is a need for new, more effective treatments.
  • Thus, concepts of specific immunotherapies such as immunogene therapy have been developed.
  • Currently, various gene therapy strategies of malignant melanoma are being evaluated in multiple clinical trials carried out all over the world.
  • They include gene modified cancer vaccines (GMTV) modified with genes encoding (i) cytokines or (ii) costimulatory molecules and dendritic cells modified with (iii) genes encoding tumor antigens or (iv) immunostimulatory factors.
  • Since January 1996 in Department of Cancer Immunology USOMS, at GreatPoland Cancer Center in Poznan, Poland a GMTV has been tested in malignant melanoma patients.
  • For the last 6 years more than 220 patients were enrolled into study of GMTV consisting of melanoma cells modified with genes encoding IL-6 and its agonistic soluble receptor (sIL-6R).
  • [MeSH-major] Cancer Vaccines / genetics. Cancer Vaccines / therapeutic use. Genetic Therapy. Melanoma / therapy
  • [MeSH-minor] Clinical Trials as Topic. Genetic Engineering. Humans. Poland / epidemiology. Vaccines, Synthetic / genetics. Vaccines, Synthetic / therapeutic use

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  • (PMID = 12094637.001).
  • [ISSN] 0030-6657
  • [Journal-full-title] Otolaryngologia polska = The Polish otolaryngology
  • [ISO-abbreviation] Otolaryngol Pol
  • [Language] pol
  • [Publication-type] English Abstract; Journal Article; Research Support, Non-U.S. Gov't; Review
  • [Publication-country] Poland
  • [Chemical-registry-number] 0 / Cancer Vaccines; 0 / Vaccines, Synthetic
  • [Number-of-references] 18
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60. Fauzdar S, Rao DD, Arthanari KK, Krishnan G, Naikmasur VG, Revanappa MM: Malignant melanoma of the mandibular gingiva. Rare Tumors; 2010;2(2):e25

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  • [Title] Malignant melanoma of the mandibular gingiva.
  • Oral malignant melanoma is an infrequent neoplasia making up less than 1% of all melanomas, which exhibits much more aggressive behavior than those found on the skin.
  • We present an aggressive case of oral malignant melanoma located on the mandibular gingiva in a 24-year-old male patient, who developed metastases to not only the regional lymph nodes but also the lungs and liver.
  • The advanced stage of the disease contraindicated any surgical intervention and palliative chemotherapy was planned.

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  • (PMID = 21139827.001).
  • [ISSN] 2036-3613
  • [Journal-full-title] Rare tumors
  • [ISO-abbreviation] Rare Tumors
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Italy
  • [Other-IDs] NLM/ PMC2994515
  • [Keywords] NOTNLM ; melanoma / mucosal melanoma. / oral malignant melanoma / oral mucosa / oral pigmentation
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61. Staudt M, Lasithiotakis K, Leiter U, Meier F, Eigentler T, Bamberg M, Tatagiba M, Brossart P, Garbe C: Determinants of survival in patients with brain metastases from cutaneous melanoma. Br J Cancer; 2010 Apr 13;102(8):1213-8
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  • [Title] Determinants of survival in patients with brain metastases from cutaneous melanoma.
  • BACKGROUND: This retrospective study aimed to identify prognostic factors in patients with brain metastases from cutaneous melanoma.
  • In all, 36.7% were candidates for local treatment (neurosurgery or stereotactic radiosurgery (SRS)).
  • Favourable independent prognostic factors were: normal pre-treatment level of serum lactate dehydrogenase (P<0.001), administered therapy (neurosurgery or SRS vs other, P=0.002), number of brain metastases (single vs multiple, P=0.032) and presence of bone metastasis (false vs true, P=0.044).
  • Candidates for local treatment (group I) had the longer median survival (9 months).
  • CONCLUSION: Applied treatment and serum lactate dehydrogenase levels were independent predictors of survival of patients with brain metastases from cutaneous melanoma.
  • Patients receiving local therapy have overall survival comparable with general stage IV melanoma patients.
  • [MeSH-major] Brain Neoplasms / secondary. Brain Neoplasms / therapy. L-Lactate Dehydrogenase / blood. Melanoma / pathology. Skin Neoplasms / drug therapy. Skin Neoplasms / pathology

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  • (PMID = 20372154.001).
  • [ISSN] 1532-1827
  • [Journal-full-title] British journal of cancer
  • [ISO-abbreviation] Br. J. Cancer
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] EC 1.1.1.27 / L-Lactate Dehydrogenase
  • [Other-IDs] NLM/ PMC2856002
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62. Kefford RF, Clingan PR, Brady B, Ballmer A, Morganti A, Hersey P: A randomized, double-blind, placebo-controlled study of high-dose bosentan in patients with stage IV metastatic melanoma receiving first-line dacarbazine chemotherapy. Mol Cancer; 2010 Mar 30;9:69
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  • [Title] A randomized, double-blind, placebo-controlled study of high-dose bosentan in patients with stage IV metastatic melanoma receiving first-line dacarbazine chemotherapy.
  • BACKGROUND: The endothelin system is implicated in the pathogenesis of melanoma.
  • We evaluated the effects of bosentan - a dual endothelin receptor antagonist - in patients receiving first-line dacarbazine therapy for stage IV metastatic cutaneous melanoma in a phase 2, proof-of-concept study.
  • RESULTS: Eligible patients had metastatic cutaneous melanoma naïve to chemotherapy or immunotherapy, no central nervous system involvement, and serum lactate dehydrogenase <1.5 x upper limit of normal.
  • Treatment comprised bosentan 500 mg twice daily or matching placebo, in addition to dacarbazine 1000 mg/m2 every three weeks.
  • Eighty patients were randomized (double-blind) and 38 in each group received study treatment.
  • Median time to tumor progression (primary endpoint) was not significantly different between the two groups (placebo, 2.8 months; bosentan, 1.6 months; bosentan/placebo hazard ratio, 1.144; 95% CI, 0.717-1.827; p = 0.5683).
  • Incidences of most adverse events and clinically relevant increases in hepatic transaminases were similar between treatment groups although hemoglobin decrease to >8 and < or = 10 g/dL and < or = 8 g/dL was more common in the bosentan group.
  • CONCLUSIONS: In patients receiving dacarbazine as first-line chemotherapy for metastatic melanoma, the addition of high-dose bosentan had no effect on time to tumor progression or other efficacy parameters.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Dacarbazine / administration & dosage. Melanoma / drug therapy. Skin Neoplasms / drug therapy. Sulfonamides / administration & dosage
  • [MeSH-minor] Double-Blind Method. Female. Humans. Kaplan-Meier Estimate. Male. Middle Aged. Neoplasm Staging

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  • (PMID = 20350333.001).
  • [ISSN] 1476-4598
  • [Journal-full-title] Molecular cancer
  • [ISO-abbreviation] Mol. Cancer
  • [Language] eng
  • [Databank-accession-numbers] ClinicalTrials.gov/ NCT01009177
  • [Publication-type] Clinical Trial, Phase II; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Sulfonamides; 7GR28W0FJI / Dacarbazine; Q326023R30 / bosentan
  • [Other-IDs] NLM/ PMC2856553
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63. Navinés R, Gómez-Gil E, Puig S, Baeza I, De Pablo J, Martín-Santos R: Depression in hospitalized patients with malignant melanoma treated with interferon-alpha-2b: primary to induced disorders. Eur J Dermatol; 2009 Nov-Dec;19(6):611-5
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  • [Title] Depression in hospitalized patients with malignant melanoma treated with interferon-alpha-2b: primary to induced disorders.
  • Our objective was to study the clinical and management differences between primary and interferon (IFN)-induced depressive disorders in malignant melanoma patients visited by the consultation-liaison team during a two year period.
  • This was a prospective study of 31 patients with malignant melanoma treated with IFN-alpha in a general teaching hospital.
  • Clinical, psychiatric variables and DSM-IV-TR diagnosis were analyzed.
  • The Clinical Global Impression Severity (CGI-S) and Improvement (CGI-I) of illness scales were administered at the time of consultation and at the end of hospitalization.
  • In patients with adjustment disorders, melanoma stage was significantly more advanced than in those with interferon-induced depressive disorder (p = 0.019).
  • The interferon-induced depressive disorders, except one who required a reduction of IFN-alpha-2b dose, were successfully treated with antidepressant drugs.
  • Clinical management and antidepressant treatment allowed the continuation of interferon therapy in malignant melanoma patients.
  • Adjustment depressive disorder was the most common psychiatric diagnosis.
  • [MeSH-major] Antineoplastic Agents / adverse effects. Depression / chemically induced. Inpatients. Interferon-alpha / adverse effects. Melanoma / drug therapy. Skin Neoplasms / drug therapy
  • [MeSH-minor] Adult. Aged. Anxiety / chemically induced. Depressive Disorder / chemically induced. Female. Hospitals, Teaching. Humans. Male. Mental Disorders / chemically induced. Middle Aged. Prospective Studies. Psychiatric Status Rating Scales. Psychotropic Drugs / therapeutic use. Recombinant Proteins. Severity of Illness Index. Surveys and Questionnaires. Treatment Outcome

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  • (PMID = 19709980.001).
  • [ISSN] 1167-1122
  • [Journal-full-title] European journal of dermatology : EJD
  • [ISO-abbreviation] Eur J Dermatol
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] France
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Interferon-alpha; 0 / Psychotropic Drugs; 0 / Recombinant Proteins; 99210-65-8 / interferon alfa-2b
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64. Osorio M, Gracia E, Rodríguez E, Saurez G, Arango Mdel C, Noris E, Torriella A, Joan A, Gómez E, Anasagasti L, González JL, Melgares Mde L, Torres I, González J, Alonso D, Rengifo E, Carr A, Pérez R, Fernández LE: Heterophilic NeuGcGM3 ganglioside cancer vaccine in advanced melanoma patients: results of a Phase Ib/IIa study. Cancer Biol Ther; 2008 Apr;7(4):488-95
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  • [Title] Heterophilic NeuGcGM3 ganglioside cancer vaccine in advanced melanoma patients: results of a Phase Ib/IIa study.
  • NeuGcGM3 ganglioside is especially attractive because it is expressed on melanoma cells but it is minimally or not expressed at all on most normal human tissues.
  • A Phase Ib/IIa clinical trial was carried out in patients with advanced cutaneous and ocular malignant melanomas, to evaluate immunogenicity and toxicity of an intramuscularly administered cancer vaccine and composed by NeuGcGM3 in a proteoliposome of Neisseria meningitides with Montanide ISA 51 as adjuvant.
  • Twenty two patients were included, twelve at dose level of 200 microg and 10 at 400 microg.
  • The first five doses were administered every other week and then monthly until 9 doses.
  • Interestingly, 3 patients developed vitiligo at the lower dose (none in the highest dose) although the nominal antigen NeuGcGM3 is not present in melanocytes.
  • Safety and immunogenicity with NeuGcGM3 vaccine treatment in advanced melanoma patients were established.
  • The prognostic value of autoimmunity and the possibilities of dissociating anti-tumor immunity from autoimmunity deserve further research.
  • [MeSH-major] Cancer Vaccines / therapeutic use. Eye Neoplasms / drug therapy. G(M3) Ganglioside / analogs & derivatives. Melanoma / drug therapy. Skin Diseases / drug therapy
  • [MeSH-minor] Adult. Aged. Bacterial Outer Membrane Proteins / immunology. Female. Humans. Immunoglobulin A / blood. Immunoglobulin A / immunology. Immunoglobulin G / blood. Immunoglobulin G / immunology. Immunoglobulin M / blood. Immunoglobulin M / immunology. Liposomes. Male. Mannitol / administration & dosage. Mannitol / analogs & derivatives. Middle Aged. Neisseria meningitidis / immunology. Oleic Acids / administration & dosage. Survival Analysis. Treatment Outcome. Vaccination. Vitiligo / immunology

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  • (PMID = 18285705.001).
  • [ISSN] 1555-8576
  • [Journal-full-title] Cancer biology & therapy
  • [ISO-abbreviation] Cancer Biol. Ther.
  • [Language] eng
  • [Publication-type] Clinical Trial, Phase I; Clinical Trial, Phase II; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Bacterial Outer Membrane Proteins; 0 / Cancer Vaccines; 0 / G(M3) Ganglioside; 0 / Immunoglobulin A; 0 / Immunoglobulin G; 0 / Immunoglobulin M; 0 / Liposomes; 0 / Oleic Acids; 0 / montanide ISA 51; 3OWL53L36A / Mannitol; 69345-49-9 / N-glycolylneuraminyllactosylceramide
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65. Kirsch A: Successful treatment of metastatic malignant melanoma with Viscum album extract (Iscador M). J Altern Complement Med; 2007 May;13(4):443-5
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  • [Title] Successful treatment of metastatic malignant melanoma with Viscum album extract (Iscador M).
  • BACKGROUND: Recent study results demonstrate possible clinical benefit from adjuvant treatment with a standardized mistletoe (Viscum album) extract in patients with malignant melanoma.
  • PATIENT AND METHOD: We present a male patient, currently 68 years of age, with one malignant melanoma at the upper part of the right arm since 1992, and another nodular melanoma at the left shoulder, first diagnosed in 1999.
  • After discovery of the second melanoma and surgical resection, the patient was exclusively treated with standardized mistletoe extract (Iscador, (R)M; Weleda AG, CH-Arlesheim, Switzerland).
  • COURSE OF THERAPY AND RESULTS: In June 1992, histologic analysis confirmed the presence of stage IA superficially spreading malignant melanoma with low infiltration of the papillary dermis in a skin excision sample from the upper part of the right arm.
  • In November 1999, another melanoma was surgically removed at the patient's right shoulder.
  • In this case, the histologic examination revealed nodular melanoma, stage IIA (pT3, pN0, M0).
  • Therapy with mistletoe extract was introduced shortly afterwards as the sole adjuvant treatment.
  • During the course of the mistletoe therapy, axillary removal of 8 lymph nodes became necessary, 3 of which proved to be metastatic.
  • First signs of a defined solitary liver metastasis in an area next to segments IV and V were detected during an abdominal ultrasound examination in September 2001.
  • The solitary liver metastasis was not resected, nor was classical antitumor treatment (chemotherapy or radiotherapy) initiated.
  • The patient continued subcutaneous treatment with Iscador M after dose adaptation to 2 mg twice weekly (0.2 mL of a 10-mg vial); the treatment is still ongoing to the present.
  • CONCLUSIONS: The use of low-dose Iscador as the sole postoperative modality for the adjuvant treatment of metastatic melanoma was extremely effective and very well tolerated in this patient.
  • [MeSH-major] Antineoplastic Agents / administration & dosage. Liver Neoplasms / drug therapy. Liver Neoplasms / secondary. Melanoma / drug therapy. Melanoma / secondary. Plant Extracts / administration & dosage. Plant Proteins / administration & dosage. Skin Neoplasms / drug therapy
  • [MeSH-minor] Adjuvants, Pharmaceutic. Aged. Humans. Male. Treatment Outcome. Viscum album

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  • (PMID = 17532738.001).
  • [ISSN] 1075-5535
  • [Journal-full-title] Journal of alternative and complementary medicine (New York, N.Y.)
  • [ISO-abbreviation] J Altern Complement Med
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Adjuvants, Pharmaceutic; 0 / Antineoplastic Agents; 0 / Plant Extracts; 0 / Plant Proteins; 0 / viscum album peptide
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66. Gray-Schopfer V, Wellbrock C, Marais R: Melanoma biology and new targeted therapy. Nature; 2007 Feb 22;445(7130):851-7
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  • [Title] Melanoma biology and new targeted therapy.
  • Melanoma is a cancer that arises from melanocytes, specialized pigmented cells that are found predominantly in the skin.
  • The incidence of melanoma is rising steadily in western populations--the number of cases worldwide has doubled in the past 20 years.
  • In its early stages malignant melanoma can be cured by surgical resection, but once it has progressed to the metastatic stage it is extremely difficult to treat and does not respond to current therapies.
  • Recent discoveries in cell signalling have provided greater understanding of the biology that underlies melanoma, and these advances are being exploited to provide targeted drugs and new therapeutic approaches.
  • [MeSH-major] Melanoma / drug therapy. Melanoma / physiopathology. Skin Neoplasms / drug therapy. Skin Neoplasms / physiopathology
  • [MeSH-minor] Animals. Cell Aging. Humans. Microphthalmia-Associated Transcription Factor / metabolism. Signal Transduction / drug effects

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  • (PMID = 17314971.001).
  • [ISSN] 1476-4687
  • [Journal-full-title] Nature
  • [ISO-abbreviation] Nature
  • [Language] eng
  • [Grant] United Kingdom / Worldwide Cancer Research / / 06-0062
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't; Review
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Microphthalmia-Associated Transcription Factor
  • [Number-of-references] 100
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67. Gaudy C, Richard MA, Folchetti G, Bonerandi JJ, Grob JJ: Randomized controlled study of electrochemotherapy in the local treatment of skin metastases of melanoma. J Cutan Med Surg; 2006 May-Jun;10(3):115-21
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  • [Title] Randomized controlled study of electrochemotherapy in the local treatment of skin metastases of melanoma.
  • BACKGROUND: Electrochemotherapy (ECT) combines intralesional injections of bleomycin with electroporation (EP), which permeabilizes tumor cells and thus increases the bleomycin efficacy at the tumor site.
  • OBJECTIVE: To assess whether EP therapy improves the local control of skin metastases of melanoma by intralesional bleomycin.
  • The secondary objective was to evaluate tolerance of the treatments.
  • PATIENTS: Patients with at least two measurable skin metastases of melanoma that were previously untreated, either in stage III with in-transit melanoma skin metastases or stage IV with no efficacy of systemic chemotherapy on these metastases.
  • DESIGN: A prospective internally controlled study with randomization of melanoma skin metastases in each individual to intralesional injections of bleomycin alone or to intralesional injections of bleomycin with EP.
  • The primary end point was the rate of complete local response per treated melanoma skin metastasis at week 12, and the secondary end point was tolerance.
  • RESULTS: Fifty-four melanoma skin metastases were treated in 12 patients (8 stage IV patients under chemotherapy and 4 stage III patients free of other treatment).
  • A local complete response was obtained in 36% (11 of 30) of melanoma skin metastases treated with bleomycin + EP and only in 8% (2 of 24) of melanoma skin metastases treated with bleomycin alone (p = .016).
  • All patients (12 of 12) reported discomfort during the EP procedure, including local pain for 9 patients (75%) at the treatment site and muscle spasm with myoclonia in 3 cases (25%).
  • CONCLUSIONS: EP increases the effect of intralesional bleomycin and improves the rate of local control in melanoma skin metastases without inducing a more systemic effect.
  • This local treatment could be useful in a palliative strategy in patients with melanoma skin metastases.
  • [MeSH-major] Antibiotics, Antineoplastic / administration & dosage. Bleomycin / administration & dosage. Electroporation. Melanoma / drug therapy. Skin Neoplasms / drug therapy
  • [MeSH-minor] Aged. Female. Humans. Male. Middle Aged. Palliative Care. Prospective Studies. Remission Induction. Treatment Outcome

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  • (PMID = 17241586.001).
  • [ISSN] 1203-4754
  • [Journal-full-title] Journal of cutaneous medicine and surgery
  • [ISO-abbreviation] J Cutan Med Surg
  • [Language] eng
  • [Publication-type] Journal Article; Randomized Controlled Trial
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antibiotics, Antineoplastic; 11056-06-7 / Bleomycin
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68. Bouguila J, Zairi I, Jablaoui Y, Haddad S, Hellali M, Azzouz E, Moustafa M, Adouani A: [Primary malignant melanoma of the nasal cavity presenting as a large tumor of the cheek]. Rev Stomatol Chir Maxillofac; 2006 Dec;107(6):474-6
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  • [Title] [Primary malignant melanoma of the nasal cavity presenting as a large tumor of the cheek].
  • [Transliterated title] Mélanome malin des fosses nasales révélé par une tuméfaction jugale.
  • INTRODUCTION: Malignant melanoma of the nasal cavity is a rare tumor usually causing unilateral nasal obstruction and nasal bleeding.
  • Diagnosis is achieved with immunohistochemistry analysis.
  • Surgery is proposed for curative treatment.
  • CASE REPORT: We report the case of a 60-year-old man with a malignant melanoma of the nasal cavity revealed by an important tumor of the cheek.
  • Because of the tumor stage, palliative chemotherapy was performed but the patient died 4 months after the diagnosis.
  • DISCUSSION: This clinical presentation of malignant melanoma of the nasal cavity, related to local spreading, is exceptional.
  • CT scan and MRI are essential for tumor staging and therapeutic decision-making.
  • [MeSH-major] Melanoma / pathology. Nasal Cavity / pathology. Nose Neoplasms / pathology

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  • (PMID = 17195003.001).
  • [ISSN] 0035-1768
  • [Journal-full-title] Revue de stomatologie et de chirurgie maxillo-faciale
  • [ISO-abbreviation] Rev Stomatol Chir Maxillofac
  • [Language] fre
  • [Publication-type] Case Reports; English Abstract; Journal Article
  • [Publication-country] France
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69. al Barbarawi M, Smith SF, Qudsieh S, Sekhon LH: Multiple cerebral and leptomeningeal metastases from ovarian carcinoma: unusual early presentation. J Clin Neurosci; 2005 Aug;12(6):697-9
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  • This report describes the first known case of multiple cerebral and leptomeningeal metastases as the initial manifestation of ovarian carcinoma in a 41-year old woman who presented with a one-week history of headache, vomiting and confusion.
  • A large ovarian tumour identified on pelvic CT scan was resected and the patient subsequently received chemotherapy and radiotherapy.
  • Unlike primary tumours such as malignant melanoma, ovarian carcinoma does not have a predilection for the central nervous system (CNS), but the rare instances with CNS involvement occur at an advanced stage of the disease.
  • Once the CNS is involved, the outcome is abysmal, even with multimodality therapy.
  • [MeSH-minor] Adult. Craniotomy / methods. Female. Humans. Magnetic Resonance Imaging / methods. Tomography, X-Ray Computed / methods

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  • (PMID = 16115553.001).
  • [ISSN] 0967-5868
  • [Journal-full-title] Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia
  • [ISO-abbreviation] J Clin Neurosci
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Scotland
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70. Whitehead RP, Moon J, McCachren SS, Hersh EM, Samlowski WE, Beck JT, Tchekmedyian NS, Sondak VK, Southwest Oncology Group: A Phase II trial of vinorelbine tartrate in patients with disseminated malignant melanoma and one prior systemic therapy: a Southwest Oncology Group study. Cancer; 2004 Apr 15;100(8):1699-704
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  • [Title] A Phase II trial of vinorelbine tartrate in patients with disseminated malignant melanoma and one prior systemic therapy: a Southwest Oncology Group study.
  • BACKGROUND: Single-agent chemotherapy with dacarbazine continues to be the standard of care for the treatment of metastatic melanoma.
  • However, there is a large population of patients who have failed first-line therapy and might benefit from additional treatment.
  • In the current study, the authors evaluated the antitumor effects and toxicity of vinorelbine therapy in patients who had failed one prior systemic therapy.
  • METHODS: Patients were required to have a histologic diagnosis of melanoma and be of Stage IV with measurable disease, a Southwest Oncology Group (SWOG) performance status (PS) of 0-2, no evidence of brain metastases, and adequate bone marrow and liver function.
  • Treatment was comprised of vinorelbine given at a dose of 30 mg/m(2)/week by intravenous bolus.
  • There were no complete or partial responses observed, for a response rate of 0 of the 21 patients studied (95% confidence interval [95% CI], 0-16%); the study closed after the first stage of accrual.
  • CONCLUSIONS: Despite impressive preclinical activity against melanoma, vinorelbine does not appear to have enough clinical activity to be of interest in previously treated patients with disseminated melanoma.
  • The group of previously treated patients may be used to evaluate new agents for the treatment of disseminated melanoma.
  • [MeSH-major] Antineoplastic Agents, Phytogenic / therapeutic use. Melanoma / drug therapy. Skin Neoplasms / drug therapy. Vinblastine / analogs & derivatives. Vinblastine / therapeutic use
  • [MeSH-minor] Adult. Aged. Disease-Free Survival. Drug Resistance, Neoplasm. Female. Humans. Injections, Intravenous. Male. Middle Aged. Neoplasm Metastasis

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  • [Copyright] Copyright 2004 American Cancer Society.
  • (PMID = 15073859.001).
  • [ISSN] 0008-543X
  • [Journal-full-title] Cancer
  • [ISO-abbreviation] Cancer
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / CA13612; United States / NCI NIH HHS / CA / CA20319; United States / NCI NIH HHS / CA / CA22433; United States / NCI NIH HHS / CA / CA32102; United States / NCI NIH HHS / CA / CA35176; United States / NCI NIH HHS / CA / CA35431; United States / NCI NIH HHS / CA / CA37981; United States / NCI NIH HHS / CA / CA38926; United States / NCI NIH HHS / CA / CA42777; United States / NCI NIH HHS / CA / CA45807; United States / NCI NIH HHS / CA / CA46441; United States / NCI NIH HHS / CA / CA58348; United States / NCI NIH HHS / CA / CA58861; United States / NCI NIH HHS / CA / CA63850; United States / NCI NIH HHS / CA / CA67575; United States / NCI NIH HHS / CA / CA76132
  • [Publication-type] Clinical Trial; Clinical Trial, Phase II; Journal Article; Multicenter Study; Research Support, U.S. Gov't, P.H.S.
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents, Phytogenic; 5V9KLZ54CY / Vinblastine; Q6C979R91Y / vinorelbine
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71. Garbe C, Eigentler TK: [Therapy of malignant melanoma at the stage of distant metastasis]. Hautarzt; 2004 Feb;55(2):195-213
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  • [Title] [Therapy of malignant melanoma at the stage of distant metastasis].
  • [Transliterated title] Therappie des malignen Melanoms im Stadium der Fernmetastasierung.
  • Treatment of melanoma in the stage of distant metastasis aims on palliation and achievement of durable tumor remission with prolongation of survival.
  • As long as metastasis is confined to one organ system and is removable, surgery remains the treatment of first choice.
  • More extensive metastasis should be treated by chemotherapy or chemoimmunotherapy.
  • As these treatments are associated with substantially higher toxicity they have been widely abandoned.
  • Combined treatment with dacarbazine and interferon-alpha obtain tumor responses or stable disease in 40-50% and objective tumor remissions in 15-20% of patients.
  • Effective cancer vaccination strategies and blockade of melanoma specific target molecules are currently developed as new treatment options.
  • [MeSH-major] Dacarbazine / analogs & derivatives. Melanoma / secondary. Melanoma / therapy. Skin Neoplasms / therapy
  • [MeSH-minor] Antineoplastic Agents / administration & dosage. Antineoplastic Agents / therapeutic use. Antineoplastic Agents, Alkylating / administration & dosage. Antineoplastic Agents, Alkylating / therapeutic use. Antineoplastic Agents, Phytogenic / administration & dosage. Antineoplastic Agents, Phytogenic / therapeutic use. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Bone Neoplasms / radiotherapy. Bone Neoplasms / secondary. Brain Neoplasms / diagnostic imaging. Brain Neoplasms / radiotherapy. Brain Neoplasms / secondary. Brain Neoplasms / surgery. Clinical Trials, Phase II as Topic. Clinical Trials, Phase III as Topic. Disease Progression. Humans. Immunotherapy. Interferon-alpha / administration & dosage. Interferon-alpha / therapeutic use. Interleukin-2 / administration & dosage. Interleukin-2 / therapeutic use. Liver Neoplasms / secondary. Liver Neoplasms / surgery. Lung Neoplasms / secondary. Lymphatic Metastasis. Neoplasm Metastasis. Nitrosourea Compounds / administration & dosage. Nitrosourea Compounds / therapeutic use. Organophosphorus Compounds / administration & dosage. Organophosphorus Compounds / therapeutic use. Palliative Care. Prognosis. Radiotherapy Dosage. Randomized Controlled Trials as Topic. Time Factors. Tomography, X-Ray Computed. Vindesine / administration & dosage. Vindesine / therapeutic use

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  • (PMID = 15043023.001).
  • [ISSN] 0017-8470
  • [Journal-full-title] Der Hautarzt; Zeitschrift fur Dermatologie, Venerologie, und verwandte Gebiete
  • [ISO-abbreviation] Hautarzt
  • [Language] ger
  • [Publication-type] Comparative Study; Journal Article; Review
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Antineoplastic Agents, Alkylating; 0 / Antineoplastic Agents, Phytogenic; 0 / Interferon-alpha; 0 / Interleukin-2; 0 / Nitrosourea Compounds; 0 / Organophosphorus Compounds; 7GR28W0FJI / Dacarbazine; GQ7JL9P5I2 / fotemustine; RSA8KO39WH / Vindesine; YF1K15M17Y / temozolomide
  • [Number-of-references] 51
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72. Loquai C, Nashan D, Metze D, Beiteke U, Rüping KW, Luger TA, Grabbe S: [Imiquimod, pegylated interferon-alpha-2b and interleukin-2 in the treatment of cutaneous melanoma metastases]. Hautarzt; 2004 Feb;55(2):176-81
Hazardous Substances Data Bank. Imiquimod .

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  • [Title] [Imiquimod, pegylated interferon-alpha-2b and interleukin-2 in the treatment of cutaneous melanoma metastases].
  • [Transliterated title] Imiquimod, pegyliertes Interferon-alpha-2b und Interleukin-2 in der Behandlung kutaner Melanommetastasen.
  • The immune system plays an important role in the defense against malignant melanoma.
  • After intralesional injections of these cytokines into cutaneous melanoma metastases, regression has been observed.
  • In view of its immunomodulating effects, imiquimod appears as an additional promising therapeutic option for treatment of malignant tumors.
  • In a case report, we present combined therapy with intralesional IL-2, pegylated IFN-alpha-2b and topical imiquimod 5% cream for disseminated cutaneous metastatic malignant melanoma stage IIIa.
  • This therapy achieved an almost complete remission.
  • In a treatment period of eight months, side effects remained tolerable.
  • After the end of therapy, no disease progression occurred during 11 months follow-up.
  • [MeSH-major] Adjuvants, Immunologic / administration & dosage. Aminoquinolines / administration & dosage. Antineoplastic Agents / administration & dosage. Interferon Inducers / administration & dosage. Interferon-alpha / administration & dosage. Interleukin-2 / administration & dosage. Melanoma / drug therapy. Skin Neoplasms / drug therapy
  • [MeSH-minor] Aged. Drug Therapy, Combination. Female. Follow-Up Studies. Humans. Injections, Intralesional. Neoplasm Metastasis. Recombinant Proteins. Time Factors

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  • (PMID = 14968329.001).
  • [ISSN] 0017-8470
  • [Journal-full-title] Der Hautarzt; Zeitschrift fur Dermatologie, Venerologie, und verwandte Gebiete
  • [ISO-abbreviation] Hautarzt
  • [Language] ger
  • [Publication-type] Case Reports; Comparative Study; Journal Article
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / Adjuvants, Immunologic; 0 / Aminoquinolines; 0 / Antineoplastic Agents; 0 / Interferon Inducers; 0 / Interferon-alpha; 0 / Interleukin-2; 0 / Recombinant Proteins; 43K1W2T1M6 / interferon alfa-2b; P1QW714R7M / imiquimod
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73. Noorda EM, Vrouenraets BC, Nieweg OE, van Geel AN, Eggermont AM, Kroon BB: Prognostic factors for survival after isolated limb perfusion for malignant melanoma. Eur J Surg Oncol; 2003 Dec;29(10):916-21
Hazardous Substances Data Bank. MELPHALAN .

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  • [Title] Prognostic factors for survival after isolated limb perfusion for malignant melanoma.
  • METHODS: All of 439 patients who underwent ILP for melanoma of the extremities were studied.
  • Ninety percent of the patients had MD Anderson stage IIB or III disease at the time of ILP.
  • RESULTS: Sixty-nine patients died within this period, 64 of metastatic melanoma.
  • The indication for ILP was an unresectable primary (n=3), a local recurrence (n=24) or adjuvant to excision of primary lesions (n=17) in patients with stage IIIB regional lymph node metastases.
  • These patients or patients with stage IIIAB melanoma with satellites and/or in-transit metastases with regional lymph node metastases had a relative risk of 4.6 (95% CI 2.0-6.6) and 3.6 (95% CI 2.1-10) of dying within 1 year from ILP, respectively (p<0.001).
  • In patients with stage IV disease (distant metastases), the relative risk was 22 (95% CI 3.8-127, p=0.001).
  • CONCLUSION: Patients with advanced limb melanoma have an increased risk of death within 1 year after ILP when regional lymph node or distant metastases are present.
  • [MeSH-major] Chemotherapy, Cancer, Regional Perfusion / methods. Melanoma / drug therapy. Skin Neoplasms / drug therapy
  • [MeSH-minor] Adolescent. Adult. Aged. Aged, 80 and over. Extremities. Female. Humans. Hyperthermia, Induced. Logistic Models. Male. Melphalan / administration & dosage. Middle Aged. Prognosis. Risk Factors. Survival Analysis. Treatment Outcome. Tumor Necrosis Factor-alpha / administration & dosage

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  • (PMID = 14624788.001).
  • [ISSN] 0748-7983
  • [Journal-full-title] European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology
  • [ISO-abbreviation] Eur J Surg Oncol
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Tumor Necrosis Factor-alpha; Q41OR9510P / Melphalan
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74. Prasad ML, Busam KJ, Patel SG, Hoshaw-Woodard S, Shah JP, Huvos AG: Clinicopathologic differences in malignant melanoma arising in oral squamous and sinonasal respiratory mucosa of the upper aerodigestive tract. Arch Pathol Lab Med; 2003 Aug;127(8):997-1002
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  • [Title] Clinicopathologic differences in malignant melanoma arising in oral squamous and sinonasal respiratory mucosa of the upper aerodigestive tract.
  • OBJECTIVE: Primary mucosal melanomas are rare tumors.
  • We compare melanomas arising in 2 histologically different mucosa, the stratified oral squamous mucosa and pseudostratified sinonasal respiratory mucosa, to investigate the clinicopathologic influence of native mucosal histology on the tumor.
  • METHODS: Clinicopathologic features of 36 melanomas arising in the squamous mucosa of the oral cavity were compared with 59 melanomas arising in the sinonasal respiratory mucosa.
  • RESULTS: The median age of patients was 61 and 63 years for oral and sinonasal melanomas, respectively, with the squamous and respiratory mucosa covering the maxilla being most frequently involved (68.7% and 66%, respectively).
  • The oral melanomas were more likely to be detected in the early in situ or microinvasive stage (4 cases vs none, P =.008) and were more frequently amelanotic (14 vs 12, P =.049) than sinonasal melanomas.
  • The sinonasal melanomas were frequently thicker (median thickness, 9 vs 2.6 mm), polypoid (29 vs none), ulcerated (57 vs 20), and necrotic (57 vs 14) than oral melanoma (P <.001).
  • Pseudopapillary architecture was more frequent in sinonasal melanomas (16 tumors vs none, P <.001), and desmoplastic melanomas were more frequent in the oral mucosa (6 vs 1, P =.005).
  • Sinonasal melanoma showed vascular and deep tissue invasion more frequently than oral melanoma; however, no significant difference in disease-specific survival was noted (median survival, 2.8 years vs 3.0 years; 5-year survival, 37% vs 35%, respectively).
  • CONCLUSION: Sinonasal melanomas demonstrated aggressive morphologic features significantly more frequently than oral melanomas; however, prognosis remained similar in both groups.
  • [MeSH-major] Carcinoma, Squamous Cell / pathology. Head and Neck Neoplasms / pathology. Maxillary Sinus Neoplasms / pathology. Melanoma / pathology. Mouth Mucosa / pathology. Mouth Neoplasms / pathology. Nose Neoplasms / pathology. Respiratory Mucosa / pathology
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Female. Humans. Male. Middle Aged. Nasal Mucosa / drug effects. Nasal Mucosa / pathology. Nasal Mucosa / surgery. Neoplasm Invasiveness / pathology. Paranasal Sinus Neoplasms / drug therapy. Paranasal Sinus Neoplasms / mortality. Paranasal Sinus Neoplasms / pathology. Paranasal Sinus Neoplasms / surgery


75. Ockenfels M, Lisch W: [Ocular complications of adjuvant interferon therapy for malignant melanoma: a review]. Hautarzt; 2003 Feb;54(2):144-7
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  • [Title] [Ocular complications of adjuvant interferon therapy for malignant melanoma: a review].
  • BACKGROUND AND OBJECTIVE: In dermatology, interferon Alfa 2 is used in adjuvant therapy of melanoma (stage IIa/b) as well as in treatment of cutaneous lymphoma or melanoma (stage III or higher).
  • We wondered if incidence and prognosis of ocular complications were elevated in patients receiving an adjuvant treatment of melanoma with interferons.
  • More than the half of these patients developed significant visual loss including retinal ischemia.
  • CONCLUSIONS: These data underscore the importance to inform patients concerning ocular adverse effects and emphasize the need to monitor the retina during adjuvant interferon therapy.
  • [MeSH-major] Antineoplastic Agents / adverse effects. Eye Diseases / chemically induced. Interferon-alpha / adverse effects. Melanoma / drug therapy. Skin Neoplasms / drug therapy
  • [MeSH-minor] Chemotherapy, Adjuvant. Humans. Recombinant Proteins. Retinal Diseases / chemically induced. Retinal Diseases / diagnosis. Vision Disorders / chemically induced. Vision Disorders / diagnosis

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  • (PMID = 12590309.001).
  • [ISSN] 0017-8470
  • [Journal-full-title] Der Hautarzt; Zeitschrift für Dermatologie, Venerologie, und verwandte Gebiete
  • [ISO-abbreviation] Hautarzt
  • [Language] ger
  • [Publication-type] English Abstract; Journal Article; Review
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Interferon-alpha; 0 / Recombinant Proteins; 76543-88-9 / interferon alfa-2a; 99210-65-8 / interferon alfa-2b
  • [Number-of-references] 15
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76. Schachter J, Brenner B, Fenig E, Gutman R, Sulkes A, Gutman H: Patterns of failure in patients with malignant melanoma treated with high-dose interferon-alpha2b in the adjuvant setting. Melanoma Res; 2003 Feb;13(1):93-6
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  • [Title] Patterns of failure in patients with malignant melanoma treated with high-dose interferon-alpha2b in the adjuvant setting.
  • The aim of this prospective study was to record the pattern of failure associated with high-dose interferon-alpha2b (IFN) adjuvant therapy after surgery.
  • It included 55 consecutive patients with stage IIB and III melanoma (median age 50 years) rendered disease-free by surgery but considered at high risk for relapse from a tertiary referral, university-affiliated medical centre.
  • Intervention consisted of IFN 20 mU/m(2) per day intravenously, 5 days a week for 4 weeks, followed by subcutaneous IFN 10 mU/m(2) per day three times a week for 48 weeks.
  • Treatment was stopped at completion of protocol, at disease progression or due to unacceptable toxicity.
  • Dose modification followed treatment-related toxicity.
  • Twenty-six of the 55 patients (47%) relapsed: 14 during treatment and 12 after completion of the protocol.
  • Eighteen of these 26 patients (69%) relapsed initially in a single organ, most commonly in soft tissue or the CNS.
  • Patients treated for stage IIB disease fared better than those treated for stage III disease, regardless of whether the regional metastases were microscopic or palpable.
  • IFN seems to be more commonly associated with a single-organ/single-metastasis pattern of failure, and more soft tissue and CNS relapses.
  • [MeSH-major] Antineoplastic Agents / administration & dosage. Interferon-alpha / administration & dosage. Melanoma / drug therapy. Skin Neoplasms / drug therapy
  • [MeSH-minor] Adolescent. Adult. Aged. Chemotherapy, Adjuvant. Disease Progression. Female. Humans. Infusions, Intravenous. Lymphatic Metastasis. Male. Middle Aged. Neoplasm Recurrence, Local / drug therapy. Neoplasm Recurrence, Local / pathology. Neoplasm Staging. Prospective Studies. Recombinant Proteins. Survival Rate. Treatment Failure

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  • (PMID = 12569291.001).
  • [ISSN] 0960-8931
  • [Journal-full-title] Melanoma research
  • [ISO-abbreviation] Melanoma Res.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Interferon-alpha; 0 / Recombinant Proteins; 99210-65-8 / interferon alfa-2b
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77. Fischer B, Knop J, Enk AH: [Experiences with therapy of stage IV metastatic malignant melanoma with "Legha Protocol" polychemoimmunotherapy]. Hautarzt; 2002 Jun;53(6):393-9
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  • [Title] [Experiences with therapy of stage IV metastatic malignant melanoma with "Legha Protocol" polychemoimmunotherapy].
  • [Transliterated title] Erfahrungen mit der Therapie des metastasierten malignen Melanoms im Stadium IV mittels Polychemoimmuntherapie nach dem "Legha-Protokoll".
  • BACKGROUND AND OBJECTIVE: Metastatic malignant melanoma (stage IV) is one of the most aggressive tumors.
  • At the moment there is no safe therapy.
  • Because of these promising trends, we decided to treat our own patients with this therapy to examine the results, the side effects and the practicability on normal dermatological wards.
  • PATIENTS/METHODS: From 1997 to 2000 we treated 28 patients with metastatic malignant melanoma with the polychemoimmunotherapy according to Legha's protocol.
  • The follow-up time is still ongoing, so we have to limit our results to this period.
  • We want to emphasize the practicability of this kind of therapy on normal dermatological wards in spite of the relatively high toxicity.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols. Immunotherapy. Melanoma / drug therapy. Neoplasm Metastasis / therapy. Skin Neoplasms / drug therapy
  • [MeSH-minor] Adult. Combined Modality Therapy. Female. Humans. Interferon-alpha / administration & dosage. Interferon-alpha / adverse effects. Interleukin-2 / administration & dosage. Interleukin-2 / adverse effects. Male. Middle Aged. Neoplasm Staging. Survival Rate. Treatment Outcome

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  • (PMID = 12132295.001).
  • [ISSN] 0017-8470
  • [Journal-full-title] Der Hautarzt; Zeitschrift für Dermatologie, Venerologie, und verwandte Gebiete
  • [ISO-abbreviation] Hautarzt
  • [Language] ger
  • [Publication-type] English Abstract; Journal Article
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / Interferon-alpha; 0 / Interleukin-2
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78. Schmid-Wendtner MH, Berking C, Baumert J, Schmidt M, Sander CA, Plewig G, Volkenandt M: Cutaneous melanoma in childhood and adolescence: an analysis of 36 patients. J Am Acad Dermatol; 2002 Jun;46(6):874-9
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  • [Title] Cutaneous melanoma in childhood and adolescence: an analysis of 36 patients.
  • Analysis of data of 6931 patients with cutaneous melanoma seen at the Department of Dermatology and Allergology at the Ludwig-Maximilians-University of Munich between 1977 and 1998 identified 36 patients in whom cutaneous melanomas developed during childhood or adolescence (age <18 years).
  • Thirty-one patients presented with nonmetastatic primary melanomas and 5 patients presented with metastatic melanoma.
  • Tumor thickness ranged from 0.24 to 7.0 mm, with a median of 1.29 mm (mean, 1.67 mm).
  • All patients with primary melanomas received surgical therapy; patients with metastatic disease received chemotherapy, radiation therapy, or both.
  • Similar to experience in adult patients, survival strongly correlated with tumor thickness and clinical stage at the time of diagnosis.
  • The data emphasize that a high index of suspicion for cutaneous melanoma is needed by clinicians assessing melanocytic lesions in children and adolescents for early diagnosis.
  • Reduction of the melanoma mortality rate in children and adolescents will be achieved through identification of patients at increased risk.
  • [MeSH-major] Melanoma / epidemiology. Melanoma / etiology. Neoplasm Recurrence, Local / epidemiology. Skin Neoplasms / epidemiology. Skin Neoplasms / etiology
  • [MeSH-minor] Adolescent. Child. Child, Preschool. Combined Modality Therapy. Female. Germany / epidemiology. Humans. Lymphatic Metastasis. Male. Medical Records. Nevus / congenital. Nevus / epidemiology. Retrospective Studies. Severity of Illness Index. Survival Analysis

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  • (PMID = 12063484.001).
  • [ISSN] 0190-9622
  • [Journal-full-title] Journal of the American Academy of Dermatology
  • [ISO-abbreviation] J. Am. Acad. Dermatol.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
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79. Eggermont AM: The role interferon-alpha in malignant melanoma remains to be defined. Eur J Cancer; 2001 Nov;37(17):2147-53
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  • [Title] The role interferon-alpha in malignant melanoma remains to be defined.
  • Because of its immunomodulatory effects, it has been extensively studied in melanoma patients.
  • Little antitumour activity has been demonstrated in metastatic stage IV melanoma, with overall response rates of 10-15%, which were not dose-related.
  • Yet, IFNalpha has been widely studied in the adjuvant setting for stage II and III disease.
  • Many trials have been underpowered, have used very heterogeneously mixed patient populations, a wide variety of doses and treatment schedules, and have suffered from early and unplanned analyses.
  • In light of the lack of impact on OS and the considerable to serious dose-dependent toxicity of IFNalpha, we do not have a clearly dose- and schedule-defined role for IFNalpha in the adjuvant setting and have no evidence for a benefit of IFNalpha in stage IV melanoma.
  • For the adjuvant setting, the main question: efficacy of very toxic high dose therapy versus efficacy of non-toxic long-term treatment will be answered by the mature data from the large US-Intergroup high-dose and EORTC intermediate-dose and long-term maintenance therapy trials.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Interferon-alpha / therapeutic use. Melanoma / drug therapy. Skin Neoplasms / drug therapy
  • [MeSH-minor] Combined Modality Therapy. Dose-Response Relationship, Drug. Humans. Neoplasm Staging. Randomized Controlled Trials as Topic. Survival Rate

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  • (PMID = 11677100.001).
  • [ISSN] 0959-8049
  • [Journal-full-title] European journal of cancer (Oxford, England : 1990)
  • [ISO-abbreviation] Eur. J. Cancer
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Interferon-alpha
  • [Number-of-references] 30
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80. Négrier S, Fervers B, Bailly C, Beckendorf V, Cupissol D, Doré JF, Dorval T, Garbay JR, Vilmer C: [Standards, Options and Recommendations (SOR): clinical practice guidelines for diagnosis, treatment and follow-up of cutaneous melanoma. Fédération Nationale des Centres de Lutte Contre le Cancer]. Bull Cancer; 2000 Feb;87(2):173-82
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  • [Title] [Standards, Options and Recommendations (SOR): clinical practice guidelines for diagnosis, treatment and follow-up of cutaneous melanoma. Fédération Nationale des Centres de Lutte Contre le Cancer].
  • [Transliterated title] Standards, Options et Recommandations (SOR) pour la prise en charge des patients atteints de mélanome cutané.
  • CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres and specialists from French Public Universities, General Hospitals and Private Clinics.
  • The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients.
  • The methodology is based on literature systematic review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery.
  • OBJECTIVES: To develop clinical practice guidelines according to the definitions of Standards, Options and Recommendations for the management of patients with cutaneous melanoma.
  • Once the guidelines were defined, the document was submitted for review to national and international independent reviewers and to the medical committees of the 20 French Cancer Centres.
  • RESULTS: The main recommendations for the management of cutaneous melanoma (CM) are:.
  • 1) The primary prevention of melanoma is based on a reduction in exposure to ultraviolet rays (solar or artificial).
  • 2) The diagnosis of CM requires the surgical removal and histological examination of the lesion (standard).
  • 3) The pathological report must include the diagnosis of primary malignant melanoma, the maximum thickness of the tumour in millimeters (Breslow), the clearance of surgical margins, the level of invasion (Clark), the presence and extension of regression and the presence of any ulceration (standard).
  • 4) The standard treatment of a primary melanoma without lymph node involvement is based on surgery that must ensure adequate margins depending on the thickness of the tumour (standard, level of evidence B).
  • 5) After surgery of a stage I melanoma, there is no indication for additional treatment outside a prospective therapeutic study (standard, level of evidence B, French Consensus Conference).
  • 6) For a local recurrence without node involvement, in the absence of other metastases, surgical excision is the standard treatment.
  • There is no indication for additional treatment outside a prospective therapeutic study (standard, level of evidence B).
  • 8) There is no standard therapeutic strategy for metastatic melanoma.
  • Conventional palliative treatment is chemotherapy with dacarbazine (level of evidence B).
  • Clinical surveillance and self-detection are indicated in all cases throughout life (standard).
  • [MeSH-major] Melanoma / pathology. Melanoma / therapy. Skin Neoplasms / pathology. Skin Neoplasms / therapy

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  • (PMID = 10705288.001).
  • [ISSN] 0007-4551
  • [Journal-full-title] Bulletin du cancer
  • [ISO-abbreviation] Bull Cancer
  • [Language] fre
  • [Publication-type] English Abstract; Guideline; Journal Article; Practice Guideline; Research Support, Non-U.S. Gov't
  • [Publication-country] FRANCE
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81. Wierzbicka-Hainaut E, Sassolas B, Mourey L, Guillot B, Bedane C, Guillet G, Tourani JM: Temozolomide and cisplatin combination in naive patients with metastatic cutaneous melanoma: results of a phase II multicenter trial. Melanoma Res; 2010 Apr;20(2):141-6
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  • [Title] Temozolomide and cisplatin combination in naive patients with metastatic cutaneous melanoma: results of a phase II multicenter trial.
  • Temozolomide (TMZ) is a second-generation alkylating agent that has recently shown some efficacy in stage IV melanoma.
  • The purpose of this study was to test the efficacy and safety of combination therapy with TMZ and cisplatin (CDDP) in patients with metastatic melanoma.
  • Chemo-naive patients with metastatic cutaneous melanoma were included in a phase II study of combined therapy with TMZ (200 mg/m/day), days 1-5, and CDDP (75 mg/m/day) on day 1.
  • The treatment was given every 28 days, for up to six cycles.
  • Our results suggest that concurrent adjunction of CDDP to TMZ regimen increases toxicity according to this schedule and does not improve the outcome of stage IV melanoma.
  • The objective response rate is close to response rates observed with single-agent chemotherapy.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Melanoma / drug therapy. Skin Neoplasms / drug therapy

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  • (PMID = 20075758.001).
  • [ISSN] 1473-5636
  • [Journal-full-title] Melanoma research
  • [ISO-abbreviation] Melanoma Res.
  • [Language] eng
  • [Publication-type] Clinical Trial, Phase II; Journal Article; Multicenter Study
  • [Publication-country] England
  • [Chemical-registry-number] 7GR28W0FJI / Dacarbazine; 85622-93-1 / temozolomide; Q20Q21Q62J / Cisplatin
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82. Weber JS, Zarour H, Redman B, Trefzer U, O'Day S, van den Eertwegh AJ, Marshall E, Wagner S: Randomized phase 2/3 trial of CpG oligodeoxynucleotide PF-3512676 alone or with dacarbazine for patients with unresectable stage III and IV melanoma. Cancer; 2009 Sep 1;115(17):3944-54
Hazardous Substances Data Bank. DACARBAZINE .

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  • [Title] Randomized phase 2/3 trial of CpG oligodeoxynucleotide PF-3512676 alone or with dacarbazine for patients with unresectable stage III and IV melanoma.
  • BACKGROUND: The primary objective of this phase 2 study was to assess the objective response rate (complete response [CR] + partial responses [PR]), by Response Evaluation Criteria in Solid Tumors, of PF-3512676, a CpG oligodeoxynucleotide, alone in 2 doses or in combination with dacarbazine (DTIC) in patients with unresectable stage IIIB/C or stage IV malignant melanoma, with the aim of selecting an arm to take forward to a phase 3 portion of the study.
  • METHODS: A total of 184 patients were randomized to 1 of 4 treatments: PF-3512676 10 mg (low dose), at 40 mg (high dose), 40 mg plus DTIC (850 mg/m(2)), or DTIC (850 mg/m(2)) alone.
  • Patients received PF-3512676 subcutaneously weekly in a 3-week cycle and received DTIC intravenously on the first week of the cycle.
  • RESULTS: The objective response rate (PR or CR, confirmed or unconfirmed) in the 40 mg + DTIC arm was 16% (7 patients) compared with 8% (3 patients) with DTIC alone.
  • Best response of CR or PR or stable disease (SD), with no minimum duration defined for SD, was achieved by 15 (33%) patients in the 40 mg + DTIC arm, 15 (38%) patients in the DTIC-only arm, 8 (17%) patients in the 10-mg arm, and 9 (20%) patients in the 40-mg arm.
  • The most frequently reported adverse events were classified as local injection site reactions or systemic flu-like symptoms, specifically fatigue, rigors, and pyrexia.
  • [MeSH-major] Dacarbazine / administration & dosage. Melanoma / drug therapy. Oligodeoxyribonucleotides / therapeutic use. Skin Neoplasms / drug therapy
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Cytokines / analysis. Female. Humans. Male. Middle Aged. Survival Analysis. Treatment Outcome

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  • (PMID = 19536884.001).
  • [ISSN] 0008-543X
  • [Journal-full-title] Cancer
  • [ISO-abbreviation] Cancer
  • [Language] eng
  • [Publication-type] Clinical Trial, Phase II; Clinical Trial, Phase III; Journal Article; Multicenter Study; Randomized Controlled Trial
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Cytokines; 0 / Oligodeoxyribonucleotides; 0 / ProMune; 7GR28W0FJI / Dacarbazine
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83. Maeda Y, Ito F, Nakazawa H, Tomoe H, Aiba M, Tanabe K: Penile malignant melanoma in a hemodialysis patient. Int J Urol; 2008 Aug;15(8):741-3
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  • [Title] Penile malignant melanoma in a hemodialysis patient.
  • A patient who was receiving hemodialysis treatment developed melanotic macules on the surface of the penis in 2002 and showed a tumor-like mass in the same region in July 2006.
  • The patient presented with a pedunculated tumor of 3 cm in diameter on the right side of his penis.
  • The tumor was resected for biopsy and was diagnosed as malignant melanoma.
  • The melanoma was in stage IIIB with pT4 N1 M0.
  • A computed tomography scan in the 10th postoperative month did not find any additional metastatic foci or recurrence of the tumor.
  • Therefore, particularly in dialysis patients, immune therapy might be favored over anticancer drug treatment.
  • [MeSH-major] Melanoma / pathology. Penile Neoplasms / pathology. Renal Dialysis

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  • (PMID = 18786196.001).
  • [ISSN] 1442-2042
  • [Journal-full-title] International journal of urology : official journal of the Japanese Urological Association
  • [ISO-abbreviation] Int. J. Urol.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Australia
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84. Elias EG, Zapas JL, McCarron EC, Beam SL, Hasskamp JH, Culpepper WJ: Sequential administration of GM-CSF (Sargramostim) and IL-2 +/- autologous vaccine as adjuvant therapy in cutaneous melanoma: an interim report of a phase II clinical trial. Cancer Biother Radiopharm; 2008 Jun;23(3):285-91
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  • [Title] Sequential administration of GM-CSF (Sargramostim) and IL-2 +/- autologous vaccine as adjuvant therapy in cutaneous melanoma: an interim report of a phase II clinical trial.
  • Granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-2 (IL-2) are 2 cytokines with distinct mechanisms of action that complement one another in the adjuvant management of melanoma.
  • Forty-five patients with high-risk melanoma were enrolled in an open-label, single-arm, phase II clinical trial to examine the safety, tolerability, and effectiveness of this combination.
  • After potentially curative surgery, each patient received 12 months of GM-CSF 125 microg/m2/d subcutaneously (SC) for 14 days followed by IL-2, 9 million IU/m2/d SC for 4 days (given every other cycle from months 7-12), followed by 10 days of no treatment.
  • In addition, patients who had tumors yielding an adequate number of live cells received autologous melanoma vaccines.
  • Thirty-two patients are alive: 9 of 13 with stage IV resected melanoma, 16 of 25 with stage III disease, and 7 of 7 with stage II disease.
  • Adjuvant use of sequential GM-CSF and IL-2 +/- autologous vaccine was well tolerated with good patient compliance and seemed to benefit high-risk patients with surgically resected melanoma.
  • [MeSH-major] Cancer Vaccines / therapeutic use. Granulocyte-Macrophage Colony-Stimulating Factor / administration & dosage. Interleukin-2 / genetics. Melanoma / drug therapy. Skin Neoplasms / drug therapy
  • [MeSH-minor] Adolescent. Adult. Aged. Combined Modality Therapy. Disease-Free Survival. Female. Humans. Male. Middle Aged. Recombinant Proteins

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  • (PMID = 18593361.001).
  • [ISSN] 1557-8852
  • [Journal-full-title] Cancer biotherapy & radiopharmaceuticals
  • [ISO-abbreviation] Cancer Biother. Radiopharm.
  • [Language] eng
  • [Publication-type] Clinical Trial, Phase II; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Cancer Vaccines; 0 / Interleukin-2; 0 / Recombinant Proteins; 123774-72-1 / sargramostim; 83869-56-1 / Granulocyte-Macrophage Colony-Stimulating Factor
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85. von Euler H, Sadeghi A, Carlsson B, Rivera P, Loskog A, Segall T, Korsgren O, Tötterman TH: Efficient adenovector CD40 ligand immunotherapy of canine malignant melanoma. J Immunother; 2008 May;31(4):377-84
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  • [Title] Efficient adenovector CD40 ligand immunotherapy of canine malignant melanoma.
  • Cutaneous canine melanomas are usually benign in contrast to human malignant melanoma.
  • Surgery and to a lesser extent radiotherapy and chemotherapy are widely adopted treatments but are seldom curative in advanced stages.
  • The similarities between human and canine melanoma make spontaneous canine melanoma an excellent disease model for exploring novel therapies.
  • Herein, we report the first 2 adenovector CD40L immunogene (AdCD40L) treatments of aggressive canine malignant melanoma.
  • Case no. 1 was an advanced stage III oral melanoma that was cured from malignant melanoma with 2 intratumor AdCD40L injections before cytoreductive surgery.
  • After treatment, the tumor tissue was infiltrated with T lymphocytes and B lymphocytes suggesting immune activation.
  • This dog survived 401 days after the first round of gene therapy and was free of melanoma at autopsy.
  • Case no. 2 had a conjunctival malignant melanoma with a rapid progression.
  • One hundred and twenty days after start of gene therapy and 60 days after the last injection, the tumor had regressed dramatically, and the dog had a minimal tumor mass and no signs of progression or metastasis.
  • Our results indicate that AdCD40L immunogene therapy is beneficial in canine malignant melanoma and could be considered for human malignant melanoma as well.
  • [MeSH-major] CD40 Ligand / immunology. CD40 Ligand / therapeutic use. Conjunctival Neoplasms / veterinary. Dog Diseases / therapy. Immunotherapy, Active. Melanoma / veterinary. Mouth Neoplasms / veterinary

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  • (PMID = 18391758.001).
  • [ISSN] 1524-9557
  • [Journal-full-title] Journal of immunotherapy (Hagerstown, Md. : 1997)
  • [ISO-abbreviation] J. Immunother.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 147205-72-9 / CD40 Ligand; 82115-62-6 / Interferon-gamma
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86. Raizer JJ, Hwu WJ, Panageas KS, Wilton A, Baldwin DE, Bailey E, von Althann C, Lamb LA, Alvarado G, Bilsky MH, Gutin PH: Brain and leptomeningeal metastases from cutaneous melanoma: survival outcomes based on clinical features. Neuro Oncol; 2008 Apr;10(2):199-207
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  • [Title] Brain and leptomeningeal metastases from cutaneous melanoma: survival outcomes based on clinical features.
  • Brain metastases (BM) are among the most devastating and debilitating complications of melanoma.
  • This retrospective study was conducted to gain a better understanding of patient and disease characteristics that have the greatest impact on overall survival in melanoma patients with BM; therapeutic interventions were also assessed.
  • The records of all patients diagnosed with cutaneous melanoma and BM who were seen at Memorial Sloan-Kettering Cancer Center between 1991 and 2001 were retrospectively reviewed.
  • A variety of factors, including age at diagnosis of stage IV disease, gender, race, disease stage at diagnosis, presence of BM at diagnosis of stage IV disease, neurologic symptoms, radiographic findings, number of BM, status and site(s) of extracranial metastasis, and treatment modalities, were analyzed for correlation with overall survival using univariate and multivariate Cox regression models.
  • On univariate analysis, seven patient and disease characteristics were significantly associated with poorer survival: age > 65 years, extracranial metastases, BM at stage IV diagnosis, neurologic symptoms, four or more BM, hydrocephalus, and leptomeningeal metastases.
  • Of these, age, extracranial metastasis, neurologic symptoms, and number of BM were significantly associated with poorer survival in a multivariate analysis.
  • Multivariate analysis of treatment modalities suggested that patients who had surgery, radiosurgery, or chemotherapy with temozolomide had improved survival outcomes, although this analysis has limitations.
  • The prognostic factors identified in this retrospective study should be considered when making treatment decisions for patients with BM and used as stratification factors in future clinical trials.
  • [MeSH-major] Brain Neoplasms / secondary. Melanoma / secondary. Meningeal Neoplasms / secondary. Skin Neoplasms / pathology

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  • (PMID = 18287337.001).
  • [ISSN] 1522-8517
  • [Journal-full-title] Neuro-oncology
  • [ISO-abbreviation] Neuro-oncology
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Other-IDs] NLM/ PMC2613822
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87. Bourguignon R, Paquet P, Quatresooz P, Piérard GE: [How I treat ... lentigo maligna by topical imiquimod]. Rev Med Liege; 2005 Sep;60(9):691-4
ORBi (University of Liege). Free full Text at ORBi .

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  • [Transliterated title] Comment je traite ... un lentigo malin par l'imiquimod topique (Aldara).
  • Lentigo maligna is a special form of in situ cutaneous melanoma that develops on the face of sun worshipers.
  • [MeSH-major] Aminoquinolines / therapeutic use. Antineoplastic Agents / therapeutic use. Hutchinson's Melanotic Freckle / drug therapy. Skin Neoplasms / drug therapy

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  • (PMID = 16265961.001).
  • [ISSN] 0370-629X
  • [Journal-full-title] Revue médicale de Liège
  • [ISO-abbreviation] Rev Med Liege
  • [Language] fre
  • [Publication-type] Case Reports; English Abstract; Journal Article
  • [Publication-country] Belgium
  • [Chemical-registry-number] 0 / Aminoquinolines; 0 / Antineoplastic Agents; 99011-02-6 / imiquimod
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88. Hu WH, Xie FY, Fang SH, Jiao JJ, Yan C, Peng WJ, Fu XY, Zhang F: [Cancer of the nasal cavity]. Zhonghua Zhong Liu Za Zhi; 2005 Feb;27(2):117-21
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  • [Title] [Cancer of the nasal cavity].
  • The 5-year survival rate was 55.8% in squamous-cell carcinoma, 44.0% in adenocarcinoma, 59.7% in undifferentiated carcinoma, 76.3% in adenoid cystic carcinoma, 71.4% in mucoepidermoid carcinoma, 25.0% in rhabdomyosarcoma, 26.7% in malignant melanoma, 50.0% in neuroblastoma (P > 0.05).
  • The 5-year survival rate was 73.8% in patients whose cancer completely disappeared after treatment.
  • It was 41.6% in patients whose cancer incompletely disappeared, and 34.3% in patients whose cancer remained refractory (P < 0.01).
  • The 5-year survival was 78.3% in stage I disease, 56.4% in stage II disease, 54.2% in stage III and 35.9% in stage IV (P < 0.05).
  • That with chemotherapy only was 25.0% whereas that of patients treated with combination treatment was 61.8% (P > 0.05).
  • CONCLUSION: Clinical stage, immediate therapeutic response and involvement of sphenoidal or maxillary sinus; but not the pathologic type, the presence of cervical metastasis nor the method of treatment, are the factors affecting the prognosis of patients with nasal carcinoma.
  • [MeSH-major] Nasal Cavity. Nose Neoplasms / mortality. Nose Neoplasms / therapy
  • [MeSH-minor] Adolescent. Adult. Aged. Aged, 80 and over. Child. Combined Modality Therapy. Female. Humans. Male. Middle Aged. Multivariate Analysis. Prognosis. Survival Rate

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  • (PMID = 15946555.001).
  • [ISSN] 0253-3766
  • [Journal-full-title] Zhonghua zhong liu za zhi [Chinese journal of oncology]
  • [ISO-abbreviation] Zhonghua Zhong Liu Za Zhi
  • [Language] chi
  • [Publication-type] English Abstract; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] China
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89. Reiriz AB, Richter MF, Fernandes S, Cancela AI, Costa TD, Di Leone LP, Schwartsmann G: Phase II study of thalidomide in patients with metastatic malignant melanoma. Melanoma Res; 2004 Dec;14(6):527-31
Hazardous Substances Data Bank. THALIDOMIDE .

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  • [Title] Phase II study of thalidomide in patients with metastatic malignant melanoma.
  • We evaluated the single-agent antitumour activity and toxicity profile of thalidomide in patients with metastatic malignant melanoma, as well as its plasma pharmacokinetics and pharmacodynamic effects [vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (b-FGF) levels].
  • A two-stage Gehan method was used with a stopping rule after 14 consecutive non-responding patients.
  • Other toxicities were oedema, neuropathy, dry skin, dry mouth, tremor and fatigue.
  • The plasma pharmacokinetics of thalidomide were comparable with those of previous studies in normal volunteers and in patients with advanced prostate cancer.
  • Serum levels of b-FGF and VEGF did not change significantly following drug administration.
  • In conclusion, thalidomide showed poor activity, but acceptable toxicity, in patients with metastatic melanoma.
  • [MeSH-major] Angiogenesis Inhibitors / therapeutic use. Melanoma / drug therapy. Neoplasm Recurrence, Local / drug therapy. Neovascularization, Pathologic / prevention & control. Skin Neoplasms / drug therapy. Thalidomide / therapeutic use
  • [MeSH-minor] Administration, Oral. Adult. Aged. Drug Administration Schedule. Female. Fibroblast Growth Factor 2 / metabolism. Humans. Maximum Tolerated Dose. Middle Aged. Survival Rate. Treatment Outcome. Vascular Endothelial Growth Factor A / metabolism

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  • (PMID = 15577325.001).
  • [ISSN] 0960-8931
  • [Journal-full-title] Melanoma research
  • [ISO-abbreviation] Melanoma Res.
  • [Language] eng
  • [Publication-type] Clinical Trial; Clinical Trial, Phase II; Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Angiogenesis Inhibitors; 0 / Vascular Endothelial Growth Factor A; 103107-01-3 / Fibroblast Growth Factor 2; 4Z8R6ORS6L / Thalidomide
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90. Boria PA, Murry DJ, Bennett PF, Glickman NW, Snyder PW, Merkel BL, Schlittler DL, Mutsaers AJ, Thomas RM, Knapp DW: Evaluation of cisplatin combined with piroxicam for the treatment of oral malignant melanoma and oral squamous cell carcinoma in dogs. J Am Vet Med Assoc; 2004 Feb 1;224(3):388-94
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  • [Title] Evaluation of cisplatin combined with piroxicam for the treatment of oral malignant melanoma and oral squamous cell carcinoma in dogs.
  • OBJECTIVE: To determine the maximum tolerated dose (MTD) of cisplatin administered with piroxicam, the antitumor activity and toxicity of cisplatin combined with piroxicam in dogs with oral malignant melanoma (OMM) and oral squamous cell carcinoma (SCC), and the effects of piroxicam on the pharmacokinetics of cisplatin in dogs with tumors.
  • PROCEDURE: Dogs were treated with a combination of cisplatin (escalating dose with 6 hours of diuresis with saline [0.9% NaCI] solution) and piroxicam (0.3 mg/kg 10.14 mg/lb], PO, q 24 h).
  • Tumor stage and size were determined at 6-week intervals during treatment.
  • Tumor remission occurred in 5 of 9 dogs with SCC and 2 of 11 dogs with OMM.
  • The level of toxicity was acceptable, although renal function must be monitored carefully.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Carcinoma, Squamous Cell / veterinary. Cisplatin / therapeutic use. Dog Diseases / drug therapy. Melanoma / veterinary. Mouth Neoplasms / veterinary. Piroxicam / therapeutic use
  • [MeSH-minor] Animals. Anti-Inflammatory Agents, Non-Steroidal / adverse effects. Anti-Inflammatory Agents, Non-Steroidal / therapeutic use. Antineoplastic Combined Chemotherapy Protocols / adverse effects. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Dogs. Dose-Response Relationship, Drug. Drug Evaluation / veterinary. Drug Interactions. Female. Male. Prospective Studies. Remission Induction. Treatment Outcome

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  • (PMID = 14765798.001).
  • [ISSN] 0003-1488
  • [Journal-full-title] Journal of the American Veterinary Medical Association
  • [ISO-abbreviation] J. Am. Vet. Med. Assoc.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Anti-Inflammatory Agents, Non-Steroidal; 0 / Antineoplastic Agents; 13T4O6VMAM / Piroxicam; Q20Q21Q62J / Cisplatin
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91. Neuber K, Reinhold U, Deutschmann A, Pföhler C, Mohr P, Pichlmeier U, Baumgart J, Hauschild A: Second-line chemotherapy of metastatic malignant melanoma with intravenous treosulfan: a phase II multicentre trial. Melanoma Res; 2003 Feb;13(1):81-5
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  • [Title] Second-line chemotherapy of metastatic malignant melanoma with intravenous treosulfan: a phase II multicentre trial.
  • The purpose of this multicentre phase II trial was to evaluate time to progression, survival time, rate of objective tumour response and toxicity of second-line intravenous treosulfan chemotherapy in stage IV melanoma patients.
  • Thirty-one patients with measurable stage IV malignant melanoma and prior chemotherapy with a dacarbazine-containing regimen were included.
  • Patients were evaluated for tumour response, survival time and toxicity.
  • Five patients (19%) showed no change and 21 had progressive disease after treosulfan treatment.
  • The median time to progression was 1.8 months (95% confidence interval [CI] 1.6-2.1 months) and the median overall survival was 6.5 months (95% CI 3.1-10 months).
  • The 1 year survival rate was 33.9% (95% CI 15.4-52.3%).
  • The non-haematological toxicity of this outpatient regimen was mild.
  • In conclusion, intravenous treosulfan treatment does not induce objective response rates when used as a second-line treatment of metastatic malignant melanoma.
  • [MeSH-major] Antineoplastic Agents, Alkylating / therapeutic use. Busulfan / analogs & derivatives. Busulfan / therapeutic use. Melanoma / drug therapy. Skin Neoplasms / drug therapy
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Disease Progression. Female. Humans. Infusions, Intravenous. Male. Middle Aged. Neoplasm Staging. Salvage Therapy. Survival Rate. Time Factors. Treatment Outcome

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  • (PMID = 12569289.001).
  • [ISSN] 0960-8931
  • [Journal-full-title] Melanoma research
  • [ISO-abbreviation] Melanoma Res.
  • [Language] eng
  • [Publication-type] Clinical Trial; Clinical Trial, Phase II; Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antineoplastic Agents, Alkylating; CO61ER3EPI / treosulfan; G1LN9045DK / Busulfan
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92. Rao UN, Ibrahim J, Flaherty LE, Richards J, Kirkwood JM: Implications of microscopic satellites of the primary and extracapsular lymph node spread in patients with high-risk melanoma: pathologic corollary of Eastern Cooperative Oncology Group Trial E1690. J Clin Oncol; 2002 Apr 15;20(8):2053-7
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  • [Title] Implications of microscopic satellites of the primary and extracapsular lymph node spread in patients with high-risk melanoma: pathologic corollary of Eastern Cooperative Oncology Group Trial E1690.
  • PURPOSE: To correlate the presence of extracapsular spread (ECS) of regional nodal metastases, and micrometastasis near the primary tumor, with disease outcome in the intergroup study E1690 in relation to the impact of recombinant interferon-alfa (rIFN alpha)-2b.
  • PATIENTS AND METHODS: E1690 included 642 patients with American Joint Committee on Cancer stage IIB or III cutaneous melanoma.
  • Patients were randomized into high- and low-dose rIFN alpha-2b treatment arms and an observation arm.
  • Evaluation of the primary tumor included notations regarding ulceration, mitotic activity, thickness, microscopic satellites (MS), and nodal ECS on a standardized pathology form.
  • RESULTS: Ulceration, mitotic activity, thickness, and size of tumor-bearing lymph nodes did not show a statistically significant correlation with either OS or RFS across all treatment arms.
  • Ulceration, mitotic activity, thickness, and number of positive lymph nodes had no significant effect on OS in this subset study (univariate or multivariate Cox analysis).
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Interferon-alpha / therapeutic use. Melanoma / drug therapy. Melanoma / pathology
  • [MeSH-minor] Humans. Lymphatic Metastasis. Mitotic Index. Neoplasm Staging. Recombinant Proteins. Skin Neoplasms / drug therapy. Skin Neoplasms / pathology. Survival Analysis. Ulcer

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  • (PMID = 11956265.001).
  • [ISSN] 0732-183X
  • [Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • [ISO-abbreviation] J. Clin. Oncol.
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / CA14028; United States / NCI NIH HHS / CA / CA21115; United States / NCI NIH HHS / CA / CA23318; United States / NCI NIH HHS / CA / CA32102; United States / NCI NIH HHS / CA / CA39229; United States / NCI NIH HHS / CA / CA66636
  • [Publication-type] Clinical Trial; Journal Article; Randomized Controlled Trial; Research Support, U.S. Gov't, P.H.S.
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Interferon-alpha; 0 / Recombinant Proteins; 99210-65-8 / interferon alfa-2b
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93. Taylor CW, Dorr RT, Fanta P, Hersh EM, Salmon SE: A phase I and pharmacodynamic evaluation of polyethylene glycol-conjugated L-asparaginase in patients with advanced solid tumors. Cancer Chemother Pharmacol; 2001;47(1):83-8
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  • PURPOSE: To evaluate the in vitro activity of polyethylene glycol-conjugated L-asparaginase (PEG-Lasparaginase) against fresh human tumor specimens, using the human tumor clonogenic assay (HTCA), and to perform a phase I dose-escalation clinical trial of PEG-L-asparaginase.
  • PEG-L-asparaginase was administered by intramuscular injection every 2 weeks to 28 patients with various types of advanced solid tumor malignancies.
  • At least 3 patients were evaluated at each dose level: 250 IU/m2, 500 IU/m2, 1,000 IU/m2, 1,500 IU/m2, 2,000 IU/m2.
  • RESULTS: The in vitro HTCA studies suggested good antitumor activity against malignant melanoma and multiple myeloma.
  • Patients receiving this dose level also showed more frequent grade 1, grade 2, and occasional grade 3 toxicities of fatigue/weakness, nausea/vomiting, and anorexia/ weight loss.
  • Three patients developed hypersensitivity reactions, but these were not dose related.
  • Two patients developed deep vein thromboses.
  • We saw no partial or complete responses in patients treated in this study, including 11 patients with malignant melanoma.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Asparaginase / therapeutic use. Glutaminase / therapeutic use. Neoplasms / drug therapy. Polyethylene Glycols / therapeutic use
  • [MeSH-minor] Adult. Asparagine / blood. Carcinoma, Non-Small-Cell Lung / drug therapy. Drug Screening Assays, Antitumor. Humans. Lung Neoplasms / drug therapy. Melanoma / drug therapy. Neoplasm Proteins / blood. Skin Neoplasms / drug therapy

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  • (PMID = 11221967.001).
  • [ISSN] 0344-5704
  • [Journal-full-title] Cancer chemotherapy and pharmacology
  • [ISO-abbreviation] Cancer Chemother. Pharmacol.
  • [Language] eng
  • [Publication-type] Clinical Trial; Clinical Trial, Phase I; Journal Article
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Neoplasm Proteins; 30IQX730WE / Polyethylene Glycols; 39335-03-0 / polyethylene glycol-glutaminase-asparaginase; 7006-34-0 / Asparagine; EC 3.5.1.1 / Asparaginase; EC 3.5.1.2 / Glutaminase
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94. Mishima Y, Kondoh H: Dual control of melanogenesis and melanoma growth: overview molecular to clinical level and the reverse. Pigment Cell Res; 2000;13 Suppl 8:10-22
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  • [Title] Dual control of melanogenesis and melanoma growth: overview molecular to clinical level and the reverse.
  • Utilizing increased melanin pigmentation and accentuated melanogenesis seen in malignant melanoma, we newly developed melanoma-selective boron neutron capture therapy (BNCT) after designing and synthesizing the 10B-DOPA analogue, 10B-p-boronophenylalanine (10B-BPA).
  • After multi-disciplined and extensive basic and pre-clinical investigations, we successfully treated 18 cases of human melanoma.
  • Recently, we found that accentuated synthesis of melanin monomers, richest within coated vesicles (CV) in melanoma cells, plays a critical role in attracting 10B-BPA through chemical complex formation of monomers and 10B-BPA.
  • It was soon found that melanin polymer formation can be suppressed by BPA at the chemical and cellular levels, then at the clinical level.
  • Our discovery, that single molecule 10B-BPA possesses the dual nature of eradication of melanoma with BNCT and suppression of melanin hyperpigmentation, resulted from pursuing bilateral feedback at each stage from pure science to clinical application and vice versa.
  • This also has its roots in clinical hurdles faced in treating amelanotic melanomas by 10B-BPA BNCT.
  • The transfer of tyrosinase and melanin monomer synthesis-related genes into target cancer cells has produced more effective BNCT and may lead to gBNCT for non-melanoma cancers.

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  • (PMID = 11041353.001).
  • [ISSN] 0893-5785
  • [Journal-full-title] Pigment cell research
  • [ISO-abbreviation] Pigment Cell Res.
  • [Language] ENG
  • [Publication-type] Lectures
  • [Publication-country] Denmark
  • [Chemical-registry-number] 0 / Boron Compounds; 0 / Indolequinones; 0 / Indoles; 0 / Melanins; 0 / Quinones; 3571-34-4 / dopachrome; 47E5O17Y3R / Phenylalanine; UID84303EL / 4-boronophenylalanine
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95. Schwipper V: [Malignant melanoma in the area of the head and neck]. Mund Kiefer Gesichtschir; 2000 May;4 Suppl 1:S177-86
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  • [Title] [Malignant melanoma in the area of the head and neck].
  • [Transliterated title] Malignes Melanom der Kopf-Hals-Region.
  • Malignant melanoma is one of the most frequent malignancies of the skin.
  • This is particularly true of malignant melanoma in juveniles.
  • At Fachklinik Hornheide, a tumor center specializing in skin neoplasm with patients being referred from all over Germany, the number of melanoma patients treated per year has been approximately 500-550 for the past 10 years.
  • In the present study, the state-of-the-art therapy for primary melanoma and treatment of the regional lymph node system is discussed.
  • The radical treatment formerly advocated with wide tumor resection plus radical neck dissection is no longer justified for this immunogenic malignant tumor caused by endogenic as well as exogenic factors.
  • "Sentinel lymph node" imaging by means of radioactive substances for diagnosing possible melanoma metastases in adjacent lymph nodes has changed the therapeutical concept.
  • Tumor staging by means of ultrasound, CT, MRT, or PET allows the differentiation of tumors without distant metastases and a favorable prognosis, from melanomas which have to be considered as generalized disease.
  • In addition to surgical resection of the tumor and neck dissection for removal of lymph nodes, adjuvant immunotherapy with interferon-alpha is capable of prolonging survival without a recurrence.
  • Palliative chemotherapy or immunotherapy are valuable options for cases with generalized melanoma.
  • Vaccination with a melanoma-associated antigen or dendritic cells is at an experimental stage and may become part of future treatment strategies.
  • [MeSH-major] Head and Neck Neoplasms / therapy. Melanoma / therapy. Skin Neoplasms / therapy
  • [MeSH-minor] Combined Modality Therapy. Humans. Neoplasm Staging. Prognosis

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  • (PMID = 10938658.001).
  • [ISSN] 1432-9417
  • [Journal-full-title] Mund-, Kiefer- und Gesichtschirurgie : MKG
  • [ISO-abbreviation] Mund Kiefer Gesichtschir
  • [Language] ger
  • [Publication-type] English Abstract; Journal Article; Review
  • [Publication-country] Germany
  • [Number-of-references] 43
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96. Feigl B, Faschinger C, Soyer P: Melanoma-associated retinopathy versus abnormal retinal function due to interferon-alpha/Isotretinoin therapy in cutaneous malignant melanoma. Ophthalmologica; 2000;214(4):271-6
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  • [Title] Melanoma-associated retinopathy versus abnormal retinal function due to interferon-alpha/Isotretinoin therapy in cutaneous malignant melanoma.
  • PURPOSE: To analyze whether an abnormal retinal function in patients with a cutaneous malignant melanoma was due to paraneoplastic retinopathy or due to isotretinoin or interferon-alpha.
  • METHODS: We studied 15 patients with malignant melanoma in stage IIa and IIb who are all participants in a randomized, multicentered, double-blind placebo-controlled clinical trial comparing interferon-alpha/isotretinoin versus interferon-alpha/placebo performed by the Department of Dermatology, University of Graz.
  • In 1 patient the therapy was stopped because of electrophysiological and psychophysiological pathology.
  • CONCLUSIONS: We postulate that in 1 of 15 patients, visual complaints are caused with a high probability by melanoma-associated retinopathy although, in the literature, isotretinoin is described to show similar effects on retinal function.
  • [MeSH-major] Antineoplastic Agents / adverse effects. Interferon-alpha / adverse effects. Isotretinoin / adverse effects. Melanoma / drug therapy. Paraneoplastic Syndromes / etiology. Retinal Diseases / chemically induced. Skin Neoplasms / drug therapy
  • [MeSH-minor] Aged. Color Perception. Double-Blind Method. Drug Therapy, Combination. Electroretinography. Female. Humans. Male. Night Blindness / etiology. Night Blindness / physiopathology. Prognosis. Visual Acuity. Visual Fields

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  • [Copyright] Copyright 2000 S. Karger AG, Basel.
  • (PMID = 10859510.001).
  • [ISSN] 0030-3755
  • [Journal-full-title] Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde
  • [ISO-abbreviation] Ophthalmologica
  • [Language] eng
  • [Publication-type] Case Reports; Clinical Trial; Comparative Study; Journal Article; Multicenter Study; Randomized Controlled Trial
  • [Publication-country] Switzerland
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Interferon-alpha; EH28UP18IF / Isotretinoin
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97. Sigalotti L, Covre A, Fratta E, Parisi G, Colizzi F, Rizzo A, Danielli R, Nicolay HJ, Coral S, Maio M: Epigenetics of human cutaneous melanoma: setting the stage for new therapeutic strategies. J Transl Med; 2010 Jun 11;8:56
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  • [Title] Epigenetics of human cutaneous melanoma: setting the stage for new therapeutic strategies.
  • Cutaneous melanoma is a very aggressive neoplasia of melanocytic origin with constantly growing incidence and mortality rates world-wide.
  • Epigenetic modifications (i.e., alterations of genomic DNA methylation patterns, of post-translational modifications of histones, and of microRNA profiles) have been recently identified as playing an important role in melanoma development and progression by affecting key cellular pathways such as cell cycle regulation, cell signalling, differentiation, DNA repair, apoptosis, invasion and immune recognition.
  • In this scenario, pharmacologic inhibition of DNA methyltransferases and/or of histone deacetylases were demonstrated to efficiently restore the expression of aberrantly-silenced genes, thus re-establishing pathway functions.
  • In light of the pleiotropic activities of epigenetic drugs, their use alone or in combination therapies is being strongly suggested, and a particular clinical benefit might be expected from their synergistic activities with chemo-, radio-, and immuno-therapeutic approaches in melanoma patients.
  • On this path, an important improvement would possibly derive from the development of new generation epigenetic drugs characterized by much reduced systemic toxicities, higher bioavailability, and more specific epigenetic effects.
  • [MeSH-major] Epigenesis, Genetic. Melanoma / drug therapy. Melanoma / genetics. Skin Neoplasms / drug therapy. Skin Neoplasms / genetics
  • [MeSH-minor] DNA Methylation / drug effects. Enzyme Inhibitors / pharmacology. Enzyme Inhibitors / therapeutic use. Histones / metabolism. Humans. MicroRNAs / metabolism. Prognosis. Protein Processing, Post-Translational / drug effects

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  • (PMID = 20540720.001).
  • [ISSN] 1479-5876
  • [Journal-full-title] Journal of translational medicine
  • [ISO-abbreviation] J Transl Med
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Enzyme Inhibitors; 0 / Histones; 0 / MicroRNAs
  • [Other-IDs] NLM/ PMC2901206
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98. Delage B, Fennell DA, Nicholson L, McNeish I, Lemoine NR, Crook T, Szlosarek PW: Arginine deprivation and argininosuccinate synthetase expression in the treatment of cancer. Int J Cancer; 2010 Jun 15;126(12):2762-72
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Arginine deprivation and argininosuccinate synthetase expression in the treatment of cancer.
  • Arginine, a semi-essential amino acid in humans, is critical for the growth of human cancers, particularly those marked by de novo chemoresistance and a poor clinical outcome.
  • Several tumours are arginine auxotrophic, due to variable loss of ASS1, including hepatocellular carcinoma, malignant melanoma, malignant pleural mesothelioma, prostate and renal cancer.
  • Several phase I/II clinical trials of the arginine-lowering drug, pegylated arginine deiminase, have shown encouraging evidence of clinical benefit and low toxicity in patients with ASS1-negative tumours.
  • In part, ASS1 loss is due to epigenetic silencing of the ASS1 promoter in various human cancer cell lines and tumours, and it is this silencing that confers arginine auxotrophy.
  • In relapsed ovarian cancer, this is associated with platinum refractoriness.
  • In contrast, several platinum sensitive tumours, including primary ovarian, stomach and colorectal cancer, are characterised by ASS1 overexpression, which is regulated by proinflammatory cytokines.
  • This review examines the prospects for novel approaches in the prevention, diagnosis and treatment of malignant disease based on ASS1 pathophysiology and its rate-limiting product, arginine.
  • [MeSH-major] Arginine / metabolism. Argininosuccinate Synthase / metabolism. Neoplasms / enzymology. Neoplasms / therapy

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  • (PMID = 20104527.001).
  • [ISSN] 1097-0215
  • [Journal-full-title] International journal of cancer
  • [ISO-abbreviation] Int. J. Cancer
  • [Language] eng
  • [Grant] United Kingdom / Cancer Research UK / / 12008; United Kingdom / Medical Research Council / / G0601891; United Kingdom / Cancer Research UK / / C12522/A8632
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 94ZLA3W45F / Arginine; EC 6.3.4.5 / Argininosuccinate Synthase
  • [Number-of-references] 86
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99. Valiahdi SM, Heffeter P, Jakupec MA, Marculescu R, Berger W, Rappersberger K, Keppler BK: The gallium complex KP46 exerts strong activity against primary explanted melanoma cells and induces apoptosis in melanoma cell lines. Melanoma Res; 2009 Oct;19(5):283-93
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] The gallium complex KP46 exerts strong activity against primary explanted melanoma cells and induces apoptosis in melanoma cell lines.
  • Owing to their robust accumulation of gallium, melanoma cells should be amenable to gallium-based anticancer drugs.
  • With the aim of improving the disappointingly low activity of inorganic gallium salts, we have developed the orally bioavailable gallium complex KP46 [tris(8-quinolinolato)gallium(III)] that had already been successfully studied in a phase I clinical trial.
  • To assess its therapeutic potential in malignant melanoma, its antiproliferative effects were investigated in series of human cell lines and primary explanted melanoma samples by means of the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay and the Human Tumor Cloning Assay, respectively.
  • When compared with other cell lines, the majority of melanoma cells rank among the KP46-sensitive cell lines (50% inhibitory concentration values: 0.8-3.7 micromol/l).
  • Clinically achievable concentrations of KP46 proved to be highly effective in melanoma cells from primary explants of cutaneous and lymph node metastases.
  • The effects induced by KP46 in melanoma cell lines involve cell-cycle perturbations (S-phase arrest) and apoptosis (activation of caspase-9, PARP [poly(ADP-ribose) polymerase] cleavage, formation of apoptotic bodies).
  • Thus, further studies on the therapeutic applicability of KP46 in malignant melanoma are warranted.
  • [MeSH-major] Apoptosis / drug effects. Gallium / pharmacology. Melanoma / drug therapy. Organometallic Compounds / pharmacology. Oxyquinoline / analogs & derivatives
  • [MeSH-minor] Cell Cycle / drug effects. Cell Line, Tumor. Humans. Inhibitory Concentration 50

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  • (PMID = 19584767.001).
  • [ISSN] 1473-5636
  • [Journal-full-title] Melanoma research
  • [ISO-abbreviation] Melanoma Res.
  • [Language] eng
  • [Grant] Austria / Austrian Science Fund FWF / / L 212
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Organometallic Compounds; 0 / tris(8-quinolinolato)gallium (III); 5UTX5635HP / Oxyquinoline; CH46OC8YV4 / Gallium
  • [Other-IDs] NLM/ PMC3371751; NLM/ UKMS48673
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100. Ishizone S, Koide N, Karasawa F, Akita N, Muranaka F, Uhara H, Miyagawa S: Surgical treatment for anorectal malignant melanoma: report of five cases and review of 79 Japanese cases. Int J Colorectal Dis; 2008 Dec;23(12):1257-62
MedlinePlus Health Information. consumer health - Melanoma.

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Surgical treatment for anorectal malignant melanoma: report of five cases and review of 79 Japanese cases.
  • INTRODUCTION: Anorectal malignant melanoma (AMM) is a relatively rare disease.
  • Because of its poor prognosis, the optimal surgical treatment for AMM is still controversial and difficult to determine.
  • We also review the present five cases along with 74 other Japanese cases reported between 1997 and 2006 and discuss the role of surgery in the treatment of AMM.
  • Furthermore, the outcome of AMM patients at stages 0 and I was better than that of AMM patients at stages II, III, and IV (p < 0.0001).
  • There was no significant difference in survival between AMM patients with and without adjuvant chemotherapy.
  • CONCLUSION: In conclusion, AMM patients treated by curative surgery can expect long-term survival, although the usefulness of adjuvant chemotherapy for AMM patients is controversial.
  • [MeSH-major] Anus Neoplasms / surgery. Melanoma / surgery. Rectal Neoplasms / surgery
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Anal Canal / surgery. Chemotherapy, Adjuvant. Female. Humans. Male. Middle Aged. Palliative Care. Rectum / surgery. Treatment Outcome

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  • (PMID = 18633625.001).
  • [ISSN] 0179-1958
  • [Journal-full-title] International journal of colorectal disease
  • [ISO-abbreviation] Int J Colorectal Dis
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Germany
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