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1. Gilheeney SW, Khakoo Y, Souweidane M, Wolden S, Boulad F, Dunkel IJ: Thiotepa/topotecan/carboplatin with autologous stem cell rescue in recurrent/refractory/poor prognosis pediatric malignancies of the central nervous system. Pediatr Blood Cancer; 2010 Apr;54(4):591-5
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  • [Title] Thiotepa/topotecan/carboplatin with autologous stem cell rescue in recurrent/refractory/poor prognosis pediatric malignancies of the central nervous system.
  • BACKGROUND: Thiotepa and carboplatin are known to be active in central nervous system tumors.
  • We present ten patients with recurrent or progressive central nervous system malignancies treated on a myeloablative regimen using these drugs.
  • METHODS: Treatment included: Thiotepa 300 mg/m(2) on days -8, -7, and -6; topotecan 2 mg/m(2) on days -8, -7, -6, -5, and -4; and carboplatin approximately 500 mg/m(2) (Calvert formula-area under the curve = 7) on days -5, -4, and -3.
  • Prior treatment for all patients included surgery and chemotherapy (1-7 regimens, median 2).
  • Three patients had residual disease at the time of transplant.
  • Four patients are event-free survivors at a median of 6 years (range 2.8-7.6 years) after treatment including 2/5 MB patients, 1/4 HGG patients, and the tRB/PB patient.
  • Four of the seven patients with no evidence of disease/minimal residual disease status at the time of stem cell rescue are long-term survivors versus 1/3 with measurable disease.
  • CONCLUSION: Thiotepa/topotecan/carboplatin may help consolidate remission of poor prognosis pediatric central nervous system tumors.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Central Nervous System Neoplasms / drug therapy
  • [MeSH-minor] Adolescent. Carboplatin / administration & dosage. Carboplatin / adverse effects. Child. Child, Preschool. Combined Modality Therapy. Female. Hematopoietic Stem Cell Transplantation. Humans. Male. Neoplasm Recurrence, Local / drug therapy. Prognosis. Thiotepa / administration & dosage. Thiotepa / adverse effects. Topotecan / administration & dosage. Topotecan / adverse effects. Young Adult

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  • (PMID = 19998470.001).
  • [ISSN] 1545-5017
  • [Journal-full-title] Pediatric blood & cancer
  • [ISO-abbreviation] Pediatr Blood Cancer
  • [Language] eng
  • [Publication-type] Clinical Trial; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 7M7YKX2N15 / Topotecan; 905Z5W3GKH / Thiotepa; BG3F62OND5 / Carboplatin
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2. Akyuz C, Aydin GB, Cila A, Akalan N, Soylemezoglu F, Cengiz M, Yazici N, Buyukpamukcu M: Successful use of intraventricular and intravenous rituximab therapy for refractory primary CNS lymphoma in a child. Leuk Lymphoma; 2007 Jun;48(6):1253-5
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  • [Title] Successful use of intraventricular and intravenous rituximab therapy for refractory primary CNS lymphoma in a child.
  • [MeSH-major] Antibodies, Monoclonal / administration & dosage. Central Nervous System Neoplasms / drug therapy. Lymphoma, B-Cell / drug therapy
  • [MeSH-minor] Adolescent. Antibodies, Monoclonal, Murine-Derived. Antineoplastic Agents / administration & dosage. Drug Resistance, Neoplasm / drug effects. Humans. Injections, Intravenous. Injections, Intraventricular. Male. Remission Induction. Rituximab. Treatment Failure

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  • (PMID = 17577799.001).
  • [ISSN] 1042-8194
  • [Journal-full-title] Leukemia & lymphoma
  • [ISO-abbreviation] Leuk. Lymphoma
  • [Language] eng
  • [Publication-type] Case Reports; Letter
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Murine-Derived; 0 / Antineoplastic Agents; 4F4X42SYQ6 / Rituximab
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3. Heimberger AB, Priebe W: Small molecular inhibitors of p-STAT3: novel agents for treatment of primary and metastatic CNS cancers. Recent Pat CNS Drug Discov; 2008 Nov;3(3):179-88
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  • [Title] Small molecular inhibitors of p-STAT3: novel agents for treatment of primary and metastatic CNS cancers.
  • High-grade primary and metastatic central nervous system (CNS) tumors are common, deadly, and refractory to conventional therapy and have a median survival duration of less than one year.
  • A key transcriptional factor, signal transducer and activator of transcription (STAT) 3, drives the fundamental components of tumor malignancy and metastases in the CNS.
  • The clinical implementation of drugs that specifically target malignancy within the CNS is clearly a major unmet need.
  • The mechanism of this in vivo efficacy of the STAT3 blockade agents is a combination of direct tumor cytotoxicity and immune cytotoxic clearance.
  • Given their ability to achieve good CNS penetration, these drugs will be taken forward into clinical trials for patients with CNS malignancies and as immunotherapeutic enhancers.
  • [MeSH-major] Antineoplastic Agents / pharmacology. Central Nervous System Neoplasms / drug therapy. STAT3 Transcription Factor / antagonists & inhibitors
  • [MeSH-minor] Humans. Immune Tolerance. Immunologic Factors / pharmacology. Neoplasm Metastasis. Phosphorylation

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  • (PMID = 18991807.001).
  • [ISSN] 1574-8898
  • [Journal-full-title] Recent patents on CNS drug discovery
  • [ISO-abbreviation] Recent Pat CNS Drug Discov
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / CA120813-01
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review
  • [Publication-country] United Arab Emirates
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Immunologic Factors; 0 / STAT3 Transcription Factor
  • [Number-of-references] 108
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4. Friedman HS: Temozolomide in early stages of newly diagnosed malignant glioma and neoplastic meningitis. Semin Oncol; 2000 Jun;27(3 Suppl 6):35-40
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  • Neoplastic meningitis, a refractory disorder, develops in approximately 3% to 8% of patients with systemic cancers.
  • Traditional approaches to leptomeningeal metastases, such as radiation and intrathecal chemotherapy, have limited success and a high degree of toxicity.
  • Temozolomide offers a number of potential therapeutic advantages in this disorder, including activity against a wide spectrum of human cancers that produce neoplastic meningitis and penetration of the blood-brain barrier.
  • Its efficacy, convenient dosing, and predictable safety profile make it an ideal agent for future study of these difficult-to-treat central nervous system malignancies.
  • [MeSH-major] Antineoplastic Agents, Alkylating / therapeutic use. Astrocytoma / drug therapy. Brain Neoplasms / drug therapy. Dacarbazine / analogs & derivatives. Glioma / drug therapy. Meningitis / drug therapy
  • [MeSH-minor] Animals. Clinical Trials as Topic. Humans. Mice. Mice, Nude. Neoplasm Staging. Quality of Life. Transplantation, Heterologous

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  • (PMID = 10866348.001).
  • [ISSN] 0093-7754
  • [Journal-full-title] Seminars in oncology
  • [ISO-abbreviation] Semin. Oncol.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't; Review
  • [Publication-country] UNITED STATES
  • [Chemical-registry-number] 0 / Antineoplastic Agents, Alkylating; 7GR28W0FJI / Dacarbazine; 85622-93-1 / temozolomide
  • [Number-of-references] 20
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5. Matsutani M, Japanese Pediatric Brain Tumor Study Group: Combined chemotherapy and radiation therapy for CNS germ cell tumors--the Japanese experience. J Neurooncol; 2001 Sep;54(3):311-6
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  • [Title] Combined chemotherapy and radiation therapy for CNS germ cell tumors--the Japanese experience.
  • Among intracranial germ cell tumors, nongerminomatous tumors have proved refractory to conventional treatment with surgery and irradiation.
  • Since 1983, chemotherapy has been delivered in Japan as an adjuvant therapy in patients with intracranial nongerminomatous germ cell tumors.
  • Based on our clinical experience, we undertook a multi-institutional phase II study to establish post-surgical combined chemotherapy and radiation therapy for primary germ cell tumors in the brain.
  • We adopted carboplatin-etoposide (CARB-VP) or cisplatin-etoposide (PE) combination chemotherapy for patients with germinomas and those with tumors that placed them in the intermediate prognosis group, and ifosphamide-cisplatin-etoposide (ICE) for patients with tumors that placed them in the poor prognosis group.
  • Among patients with germinoma (n = 75), the rate or complete remission after combination therapy was 92.0%; it was 67.8% for patients in the intermediate prognosis group (n = 28).
  • Tumor recurrence was noted in 9 patients with germinoma and 2 patients in the intermediate prognosis group.
  • Of 9 patients with a poor prognosis, 4 experienced disease progression during treatment and died within 10 months.
  • There were no serious complications attributable to the combination therapy.
  • Our treatment protocols are effective for patients with germinomas and those with an intermediate prognosis.
  • [MeSH-major] Central Nervous System Neoplasms / drug therapy. Central Nervous System Neoplasms / radiotherapy. Germinoma / drug therapy. Germinoma / radiotherapy. Postoperative Care. Teratoma / drug therapy. Teratoma / radiotherapy
  • [MeSH-minor] Antineoplastic Combined Chemotherapy Protocols / adverse effects. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Combined Modality Therapy. Humans. Neoplasm Recurrence, Local. Prognosis. Remission Induction

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  • (PMID = 11767296.001).
  • [ISSN] 0167-594X
  • [Journal-full-title] Journal of neuro-oncology
  • [ISO-abbreviation] J. Neurooncol.
  • [Language] eng
  • [Publication-type] Clinical Trial; Clinical Trial, Phase II; Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
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6. Sarris AH, Hagemeister F, Romaguera J, Rodriguez MA, McLaughlin P, Tsimberidou AM, Medeiros LJ, Samuels B, Pate O, Oholendt M, Kantarjian H, Burge C, Cabanillas F: Liposomal vincristine in relapsed non-Hodgkin's lymphomas: early results of an ongoing phase II trial. Ann Oncol; 2000 Jan;11(1):69-72
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  • PATIENTS AND METHODS: Eligible patients had histologically proven relapse, age > or = 16 years, normal renal function, neutrophils > 500/microliter, platelets > 50,000/microliter, and no HIV infection, central nervous system disease, or serious neuropathy.
  • The median number of prior regimens was 3 (range 1-10) and had included vincristine in all patients, of whom 51% were refractory to their last regimen.
  • Grade 3-4 motor or sensory neuropathy was seen in 11, and caused termination of therapy in five patients.
  • These data, if confirmed, would suggest a potential role for liposomal vincristine in the combination therapy of previously untreated patients with NHL.

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  • (PMID = 10690390.001).
  • [ISSN] 0923-7534
  • [Journal-full-title] Annals of oncology : official journal of the European Society for Medical Oncology
  • [ISO-abbreviation] Ann. Oncol.
  • [Language] ENG
  • [Grant] United States / NCI NIH HHS / CA / CA-16672
  • [Publication-type] Clinical Trial; Clinical Trial, Phase II; Journal Article; Research Support, U.S. Gov't, P.H.S.
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antineoplastic Agents, Phytogenic; 0 / Drug Carriers; 0 / Liposomes; 5J49Q6B70F / Vincristine
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7. Benesch M, Siegler N, Hoff Kv, Lassay L, Kropshofer G, Müller H, Sommer C, Rutkowski S, Fleischhack G, Urban C: Safety and toxicity of intrathecal liposomal cytarabine (Depocyte) in children and adolescents with recurrent or refractory brain tumors: a multi-institutional retrospective study. Anticancer Drugs; 2009 Oct;20(9):794-9
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Safety and toxicity of intrathecal liposomal cytarabine (Depocyte) in children and adolescents with recurrent or refractory brain tumors: a multi-institutional retrospective study.
  • This retrospective study aimed to evaluate the safety and toxicity of intrathecal liposomal cytarabine (Depocyte) in children and adolescents with refractory or recurrent brain tumors.
  • Nineteen heavily pretreated patients (males, n = 14; females, n = 5; median age at diagnosis 8.5 years; range, 1.4-22 years) were given intrathecal liposomal cytarabine on a compassionate use basis for recurrent refractory medulloblastoma (n = 12), mixed germ cell tumor (n = 2), central nervous system primitive neuroectodermal tumors of the pons (n = 1), anaplastic ependymoma (n = 1), anaplastic oligodendroglioma (n = 1), atypical teratoid rhabdoid tumor (n = 1), or rhabdoid papillary meningioma (n = 1).
  • Duration of treatment ranged from (1/2) to 10 months.
  • Eleven patients (57.9%) did not show any side effects, whereas eight patients (42.1%) developed side effects related to either chemical arachnoiditis (n = 4) or neurological progression (n = 2).
  • Less typical treatment-related symptoms (e.g. lethargy, ataxia, and slurred speech) were observed in two patients.
  • Treatment with intrathecal liposomal cytarabine was discontinued twice because of side effects.
  • [MeSH-major] Antimetabolites, Antineoplastic / adverse effects. Brain Neoplasms / drug therapy. Cytarabine / administration & dosage. Cytarabine / adverse effects
  • [MeSH-minor] Adolescent. Child. Child, Preschool. Compassionate Use Trials. Delayed-Action Preparations. Drug Resistance, Neoplasm. Female. Humans. Infant. Injections, Spinal. Liposomes / administration & dosage. Male. Retrospective Studies. Salvage Therapy. Young Adult

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  • (PMID = 19617818.001).
  • [ISSN] 1473-5741
  • [Journal-full-title] Anti-cancer drugs
  • [ISO-abbreviation] Anticancer Drugs
  • [Language] eng
  • [Publication-type] Clinical Trial; Journal Article; Multicenter Study
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antimetabolites, Antineoplastic; 0 / Delayed-Action Preparations; 0 / Liposomes; 04079A1RDZ / Cytarabine
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8. Koukourakis GV, Kouloulias V, Zacharias G, Papadimitriou C, Pantelakos P, Maravelis G, Fotineas A, Beli I, Chaldeopoulos D, Kouvaris J: Temozolomide with radiation therapy in high grade brain gliomas: pharmaceuticals considerations and efficacy; a review article. Molecules; 2009;14(4):1561-77
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Temozolomide with radiation therapy in high grade brain gliomas: pharmaceuticals considerations and efficacy; a review article.
  • Malignant gliomas (glioblastoma multiforme and anaplastic astrocytoma) which have a combined incidence of 5-8/100,000 population, represent the most common primary central nervous system tumors.
  • The treatment outcomes even with aggressive approach including surgery, radiation therapy and chemotherapy are dismal with median reported survival is less than 1 year.
  • Temozolomide is a new drug which has shown promise in treating malignant gliomas and other difficult-to-treat tumors.
  • This drug is a per os (p.o) imidazotetrazine second-generation alkylating agent which represents the leading compound in a new class of chemotherapeutic agents that enter the cerebrospinal fluid and do not require hepatic metabolism for activation.
  • Moreover, preclinical studies have evaluated the combination of temozolomide with other alkylating agents and inhibitors of the DNA repair protein O(6)-alkylguanine alkyltransferase to overcome resistance to chemotherapy in malignant glioma and malignant metastatic melanoma.
  • At the present time temozolomide is approved in the United States for the treatment of adult patients with refractory anaplastic astrocytoma and, in the European Union, for treatment of glioblastoma multiforme showing progression or recurrence after standard therapy.
  • Temozolomide's characteristics which make it a candidate for a wide range of clinical testing to evaluate the potential of combination treatments in different tumor types are its predictable bioavailability and minimal toxicity.
  • [MeSH-major] Antineoplastic Agents, Alkylating / therapeutic use. Astrocytoma. Brain Neoplasms. Dacarbazine / analogs & derivatives. Glioblastoma
  • [MeSH-minor] Combined Modality Therapy. Drug Resistance, Neoplasm. Humans. MEDLINE. Molecular Structure. Randomized Controlled Trials as Topic

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  • (PMID = 19384285.001).
  • [ISSN] 1420-3049
  • [Journal-full-title] Molecules (Basel, Switzerland)
  • [ISO-abbreviation] Molecules
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] Switzerland
  • [Chemical-registry-number] 0 / Antineoplastic Agents, Alkylating; 7GR28W0FJI / Dacarbazine; 85622-93-1 / temozolomide
  • [Number-of-references] 67
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9. Arellano-Rodrigo E, López-Guillermo A, Bessell EM, Nomdedeu B, Montserrat E, Graus F: Salvage treatment with etoposide (VP-16), ifosfamide and cytarabine (Ara-C) for patients with recurrent primary central nervous system lymphoma. Eur J Haematol; 2003 Apr;70(4):219-24
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Salvage treatment with etoposide (VP-16), ifosfamide and cytarabine (Ara-C) for patients with recurrent primary central nervous system lymphoma.
  • BACKGROUND: Survival of patients with primary central nervous system lymphoma (PCNSL) has improved with methotrexate-based combination regimens and radiotherapy (RT).
  • Very little data is available on salvage treatment at recurrence.
  • PATIENTS AND METHODS: Sixteen immunocompetent patients (13 males/three females, median age 54 yr) with refractory (one patient) or recurrent (15 patients) PCNSL, homogeneously treated at diagnosis with the cyclophosphamide, doxorubicin, vincristine, dexamethasone/carmustine, vincristine, cytarabine and methotrexate (CHOD/BVAM) and RT regimen, received etoposide (VP-16), ifosfamide and cytarabine (Ara-C) (VIA) chemotherapy as a salvage treatment.
  • The therapy was repeated every 28 d for a total of planned six cycles.
  • RESULTS: Median time between first complete response (CR) and relapse was 19 months (range: 6-46 months).
  • Five patients completed the whole VIA therapy.
  • Finally, one patient developed a severe but reversible ifosfamide encephalopathy.
  • CONCLUSION: The data presented show that the chemotherapy VIA is an effective salvage regimen for patients with recurrent PCNSL.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Brain Neoplasms / drug therapy. Lymphoma, Non-Hodgkin / drug therapy. Neoplasm Recurrence, Local / drug therapy. Salvage Therapy
  • [MeSH-minor] Adolescent. Adult. Aged. Carmustine / administration & dosage. Child, Preschool. Clinical Trials, Phase II as Topic. Combined Modality Therapy. Cranial Irradiation. Cyclophosphamide / administration & dosage. Cytarabine / administration & dosage. Dexamethasone / administration & dosage. Disease-Free Survival. Doxorubicin / administration & dosage. Drug Evaluation. Etoposide / administration & dosage. Female. Humans. Ifosfamide / administration & dosage. Life Tables. Male. Methotrexate / administration & dosage. Middle Aged. Neutropenia / chemically induced. Remission Induction. Retrospective Studies. Survival Analysis. Thrombocytopenia / chemically induced. Vincristine / administration & dosage

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  • (PMID = 12656744.001).
  • [ISSN] 0902-4441
  • [Journal-full-title] European journal of haematology
  • [ISO-abbreviation] Eur. J. Haematol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Denmark
  • [Chemical-registry-number] 04079A1RDZ / Cytarabine; 5J49Q6B70F / Vincristine; 6PLQ3CP4P3 / Etoposide; 7S5I7G3JQL / Dexamethasone; 80168379AG / Doxorubicin; 8N3DW7272P / Cyclophosphamide; U68WG3173Y / Carmustine; UM20QQM95Y / Ifosfamide; YL5FZ2Y5U1 / Methotrexate; BVAM protocol; CVAD protocol
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10. Soussain C, Suzan F, Hoang-Xuan K, Cassoux N, Levy V, Azar N, Belanger C, Achour E, Ribrag V, Gerber S, Delattre JY, Leblond V: Results of intensive chemotherapy followed by hematopoietic stem-cell rescue in 22 patients with refractory or recurrent primary CNS lymphoma or intraocular lymphoma. J Clin Oncol; 2001 Feb 01;19(3):742-9
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Results of intensive chemotherapy followed by hematopoietic stem-cell rescue in 22 patients with refractory or recurrent primary CNS lymphoma or intraocular lymphoma.
  • PURPOSE: To assess the feasibility and efficacy of intensive chemotherapy with hematopoietic stem-cell rescue (IC + HCR) in patients with refractory or recurrent primary CNS lymphoma (PCNSL) or intraocular lymphoma (IOL).
  • Intravenous clonazepam 2 mg/d was given prophylactically from the day before initiation of busulfan therapy to the day after completion of busulfan therapy.
  • Patients with refractory or recurrent PCNSL underwent IC + HCR only if they were chemosensitive to two cycles of salvage treatment with cytarabine (2 g/m(2)/d days 2 through 5 and 50 mg/m(2)/d days 1 through 5 in a 12-hour infusion) and etoposide (VP-16; 200 mg/m(2)/d days 2 through 5) (CYVE).
  • Patients with IOL refractory to high-dose methotrexate (MTX) and cytarabine entered the IC + HCR program directly.
  • RESULTS: Twenty-two patients (10 with relapses, 12 with refractory disease) were enrolled.
  • Twenty patients entered the IC + HCR program: twelve entered after CYVE treatment, seven entered directly, and one had previously been retreated with high-dose MTX.
  • Before IC, eight patients were in complete remission (CR), four were in partial remission (PR), one had stable disease, and seven had refractory disease.
  • Fourteen patients remained alive (median follow-up time, 41.5 months).
  • Seven patients had neurologic adverse events during the entire procedure.
  • CONCLUSION: IC + HCR proved feasible and effective in patients with refractory or recurrent PCNSL or IOL.
  • The entire procedure seemed to be most toxic in patients > or = 60 years.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / administration & dosage. Central Nervous System Neoplasms / therapy. Eye Neoplasms / therapy. Hematopoietic Stem Cell Transplantation. Lymphoma, Non-Hodgkin / therapy. Neoplasm Recurrence, Local / therapy
  • [MeSH-minor] Adult. Busulfan / administration & dosage. Combined Modality Therapy. Cyclophosphamide / administration & dosage. Cytarabine / administration & dosage. Disease-Free Survival. Dose-Response Relationship, Drug. Etoposide / administration & dosage. Feasibility Studies. Female. Humans. Lymphoma, B-Cell / drug therapy. Lymphoma, B-Cell / therapy. Lymphoma, Large B-Cell, Diffuse / drug therapy. Lymphoma, Large B-Cell, Diffuse / therapy. Lymphoma, Large-Cell, Immunoblastic / drug therapy. Lymphoma, Large-Cell, Immunoblastic / therapy. Lymphoma, T-Cell / drug therapy. Lymphoma, T-Cell / therapy. Male. Methotrexate / administration & dosage. Middle Aged. Nervous System Diseases / chemically induced. Salvage Therapy. Thiotepa / administration & dosage

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  • (PMID = 11157026.001).
  • [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; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 04079A1RDZ / Cytarabine; 6PLQ3CP4P3 / Etoposide; 8N3DW7272P / Cyclophosphamide; 905Z5W3GKH / Thiotepa; G1LN9045DK / Busulfan; YL5FZ2Y5U1 / Methotrexate
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11. Adams DM, Zhou T, Berg SL, Bernstein M, Neville K, Blaney SM, Children's Oncology Group: Phase 1 trial of O6-benzylguanine and BCNU in children with CNS tumors: a Children's Oncology Group study. Pediatr Blood Cancer; 2008 Mar;50(3):549-53
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  • BACKGROUND: Efficacy of nitrosoureas is limited by host repair of drug-induced alkylation.
  • O(6)-benzylguanine (O(6)-BG), an inhibitor of host alkylation repair, and BCNU were studied in children with refractory/untreatable central nervous system tumors to determine dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of BCNU administered following O(6)-BG.
  • PROCEDURE: O(6)-BG (120 mg/m(2) IV over 1 hr) was followed by BCNU (IV over 1 hr).
  • Patients in Stage 1 were accrued irrespective of prior treatment.
  • Once the MTD was exceeded, Stage II accrual was limited to less heavily pretreated patients (</= two prior chemotherapy regimens, no prior central axis radiation, no prior bone marrow transplant, and no bone marrow involvement).
  • Myelosuppression, which was cumulative in some patients receiving multiple cycles of therapy, was the predominate DLT.
  • Twenty-four patients were evaluable for response: after two courses of therapy, 6 had stable disease, 17 had progressive disease, and 1 patient had a minor response but progressed after four courses of therapy.
  • [MeSH-major] Antineoplastic Agents, Alkylating / pharmacology. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Carmustine / pharmacology. Central Nervous System Neoplasms / drug therapy. Guanine / analogs & derivatives. Neoplasm Proteins / antagonists & inhibitors. O(6)-Methylguanine-DNA Methyltransferase / antagonists & inhibitors
  • [MeSH-minor] Adolescent. Bone Marrow Diseases / chemically induced. Child. Child, Preschool. Cohort Studies. Combined Modality Therapy. DNA Repair / drug effects. DNA, Neoplasm / drug effects. Enzyme Inhibitors / administration & dosage. Enzyme Inhibitors / pharmacology. Enzyme Inhibitors / therapeutic use. Female. Humans. Male. Maximum Tolerated Dose. Salvage Therapy

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  • [Copyright] (c) 2007 Wiley-Liss, Inc.
  • (PMID = 17941066.001).
  • [ISSN] 1545-5017
  • [Journal-full-title] Pediatric blood & cancer
  • [ISO-abbreviation] Pediatr Blood Cancer
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / CA 97543; United States / NCRR NIH HHS / RR / M01 RR00188; United States / NCI NIH HHS / CA / U01 CA97552
  • [Publication-type] Clinical Trial, Phase I; Journal Article; Multicenter Study; Research Support, N.I.H., Extramural
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents, Alkylating; 0 / DNA, Neoplasm; 0 / Enzyme Inhibitors; 0 / Neoplasm Proteins; 19916-73-5 / O(6)-benzylguanine; 5Z93L87A1R / Guanine; EC 2.1.1.63 / O(6)-Methylguanine-DNA Methyltransferase; U68WG3173Y / Carmustine
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12. Langevin AM, Bernstein M, Kuhn JG, Blaney SM, Ivy P, Sun J, Chen Z, Adamson PC, Children's Oncology Group: A phase II trial of rebeccamycin analogue (NSC #655649) in children with solid tumors: a Children's Oncology Group study. Pediatr Blood Cancer; 2008 Mar;50(3):577-80
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  • BACKGROUND: Rebeccamycin Analogue (NSC #655649), a chemically synthesized glycosyl-dichloro-indolocarbazole derivative of rebeccamycin with topoisomerase inhibiting activity, has in vitro activity against pediatric tumor cell lines and tumor specimens including rhabdomyosarcoma, neuroblastoma, Ewing's sarcoma and medulloblastoma.
  • PROCEDURE: The primary objective of this trial was to determine the response rate to Rebeccamycin analogue NSC #655649 in children with refractory solid and CNS tumors.
  • Secondary objectives included further evaluation of the toxicity and pharmacokinetic profile of Rebeccamycin analogue in children with relapsed and refractory cancer.
  • Rebeccamycin analogue, 650 mg/m(2), was administered every 21 days, and could be escalated to 780 mg/m(2) in subsequent cycles to achieve a maximum plasma drug concentration >5 microg/ml.
  • [MeSH-major] Aminoglycosides / therapeutic use. Antibiotics, Antineoplastic / therapeutic use. Neoplasms / drug therapy
  • [MeSH-minor] Adolescent. Adult. Bone Marrow Diseases / chemically induced. Carbazoles. Central Nervous System Neoplasms / drug therapy. Child. Child, Preschool. Drug-Induced Liver Injury / etiology. Female. Glucosides. Humans. Infant. Infant, Newborn. Infusions, Intravenous. Male. Neoplasm Proteins / antagonists & inhibitors. Pancreatitis / chemically induced. Rhabdomyosarcoma / drug therapy. Salvage Therapy. Topoisomerase II Inhibitors

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  • [Copyright] (c) 2007 Wiley-Liss, Inc.
  • (PMID = 17610262.001).
  • [ISSN] 1545-5017
  • [Journal-full-title] Pediatric blood & cancer
  • [ISO-abbreviation] Pediatr Blood Cancer
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / CA98543; United States / NCI NIH HHS / CA / P30CA-54174
  • [Publication-type] Clinical Trial, Phase II; Journal Article; Multicenter Study; Research Support, N.I.H., Extramural
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Aminoglycosides; 0 / Antibiotics, Antineoplastic; 0 / Carbazoles; 0 / Glucosides; 0 / Neoplasm Proteins; 0 / Topoisomerase II Inhibitors; A60X6MBU6G / becatecarin
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13. Yung WK: Future directions for temozolomide therapy. Semin Oncol; 2001 Aug;28(4 Suppl 13):43-6
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  • [Title] Future directions for temozolomide therapy.
  • Although the initial indications of temozolomide (Temodar in the United States, Temodal globally; Schering Corporation, Kenilworth, NJ) therapy are for refractory central nervous system malignancies (anaplastic astrocytoma in the United States and Europe, glioblastoma multiforme in Europe), a number of clinical trials are planned or ongoing to evaluate the efficacy and safety of temozolomide in newly diagnosed glioma, oligodendroglioma, pediatric glioma, brain metastases, metastatic melanoma, and other systemic tumors.
  • Also under investigation are modifications to the temozolomide dosing schedule, other routes of administration, and treatment regimens that include temozolomide in combination with other chemotherapeutic and biologic agents.
  • Temozolomide has the potential to be a useful agent in the treatment of a variety of cancers.
  • [MeSH-major] Antineoplastic Agents, Alkylating / therapeutic use. Central Nervous System Neoplasms / drug therapy. Dacarbazine / therapeutic use
  • [MeSH-minor] Clinical Trials as Topic. Drug Administration Schedule. Drug Resistance, Neoplasm. Forecasting. Humans

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  • [Copyright] Copyright 2001 by W.B. Saunders Company.
  • (PMID = 11550138.001).
  • [ISSN] 0093-7754
  • [Journal-full-title] Seminars in oncology
  • [ISO-abbreviation] Semin. Oncol.
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents, Alkylating; 7GR28W0FJI / Dacarbazine; 85622-93-1 / temozolomide
  • [Number-of-references] 16
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14. Modak S, Cheung NK: Neuroblastoma: Therapeutic strategies for a clinical enigma. Cancer Treat Rev; 2010 Jun;36(4):307-17
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  • [Title] Neuroblastoma: Therapeutic strategies for a clinical enigma.
  • Neuroblastoma, the most common extracranial pediatric solid tumor remains a clinical enigma with outcomes ranging from cure in >90% of patients with locoregional tumors with little to no cytotoxic therapy, to <30% for those >18months of age at diagnosis with metastatic disease despite aggressive multimodality therapy.
  • Recent research has shed light on the biology of neuroblastoma allowing more accurate stratification of patients which has permitted reducing or withholding cytotoxic therapy without affecting outcome for low-risk patients.
  • However, for children with high-risk disease, the development of newer therapeutic strategies is necessary.
  • Current surgery and radiotherapy techniques in conjunction with induction chemotherapy have greatly reduced the risk of local relapse.
  • However, refractory or recurrent osteomedullary disease occurs in most patients with high-risk neuroblastoma.
  • Toxicity limits for high-dose chemotherapy appear to have been reached without further clinical benefit.
  • Radioimmunotherapy appears to be a critical component of a recent, successful regimen for treating patients who relapse in the central nervous system, a possible sanctuary site.
  • The identification of newer tumor targets and the harnessing of cell-mediated immunotherapy may generate novel therapeutic approaches.
  • It is likely that a combination of therapeutic modalities will be required to improve survival and cure rates.
  • [MeSH-major] Neuroblastoma / therapy
  • [MeSH-minor] 3-Iodobenzylguanidine / therapeutic use. Adoptive Transfer. Angiogenesis Inhibitors / therapeutic use. Antibodies, Monoclonal / therapeutic use. Humans. Immunotherapy. Neoplasm Staging

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  • [Copyright] 2010. Published by Elsevier Ltd.
  • (PMID = 20227189.001).
  • [ISSN] 1532-1967
  • [Journal-full-title] Cancer treatment reviews
  • [ISO-abbreviation] Cancer Treat. Rev.
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / CA106450; United States / NCI NIH HHS / CA / CA134274; United States / NCI NIH HHS / CA / CA61017; United States / NCI NIH HHS / CA / CA72868
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review
  • [Publication-country] Netherlands
  • [Chemical-registry-number] 0 / Angiogenesis Inhibitors; 0 / Antibodies, Monoclonal; 35MRW7B4AD / 3-Iodobenzylguanidine
  • [Number-of-references] 166
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15. Takasu S, Wakabayashi T, Kajita Y, Hatano N, Hatano H, Usui T, Kinoshita T, Yoshida J: [Effectiveness of DeVIC chemotherapy for recurrent primary central nervous system lymphoma]. No Shinkei Geka; 2000 Sep;28(9):789-94
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  • [Title] [Effectiveness of DeVIC chemotherapy for recurrent primary central nervous system lymphoma].
  • Six cases with recurrent or refractory primary central nervous system lymphoma were treated with a new chemotherapeutic regimen "DeVIC (dexamethasone, VP16, ifosfamide, carboplatin)".
  • Five recurrent cases had a remission period for an average of 18 months after initial treatment, but relapse occurred.
  • One refractory case had no response after initial treatment.
  • Then these 6 cases were treated with 1-3 courses of DeVIC chemotherapy at intervals of 4 weeks.
  • One case showed no response after 1 course of DeVIC chemotherapy.
  • DeVIC chemotherapy produced a high response rate for recurrent central nervous system lymphoma, but re-relapse occurred after only a few months.
  • The establishment of maintenance chemotherapy is required.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Brain Neoplasms / drug therapy. Lymphoma / drug therapy
  • [MeSH-minor] Adolescent. Adult. Aged. Carboplatin / administration & dosage. Combined Modality Therapy. Dexamethasone / administration & dosage. Etoposide / administration & dosage. Female. Humans. Ifosfamide / administration & dosage. Male. Middle Aged. Neoplasm Recurrence, Local. Remission Induction. Salvage Therapy. Treatment Outcome

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  • (PMID = 11025878.001).
  • [ISSN] 0301-2603
  • [Journal-full-title] No shinkei geka. Neurological surgery
  • [ISO-abbreviation] No Shinkei Geka
  • [Language] jpn
  • [Publication-type] Case Reports; Clinical Trial; English Abstract; Journal Article
  • [Publication-country] JAPAN
  • [Chemical-registry-number] 6PLQ3CP4P3 / Etoposide; 7S5I7G3JQL / Dexamethasone; BG3F62OND5 / Carboplatin; UM20QQM95Y / Ifosfamide; ICE protocol 2
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16. Namba Y, Kijima T, Yokota S, Niinaka M, Kawamura S, Iwasaki T, Takeda Y, Kimura H, Okada T, Yamaguchi T, Nakagawa M, Okumura Y, Maeda H, Ito M: Gefitinib in patients with brain metastases from non-small-cell lung cancer: review of 15 clinical cases. Clin Lung Cancer; 2004 Sep;6(2):123-8
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  • The objective tumor response rate (60%; 9 of 15 patients) for BM was the same as for primary tumors.
  • The median time to response of BM was 26 days.
  • One patient with stable primary tumor also exhibited partial response in BM with this monotherapy.
  • Central nervous system toxicities were not observed during the treatment.
  • Four of the 9 BM responders are still under treatment with neither adverse events nor disease progression.
  • Two discontinued the treatment because of severe hepatic toxicity and 3 died because of acquired resistance in pulmonary lesions, even though partial response was observed in the BMs.
  • Molecular targeted therapy against EGFR could be an option for the treatment of BM from NSCLC refractory to conventional chemotherapy plus radiation therapy because it has demonstrated a distinct therapeutic potential against BM compared with primary lung tumor and extracranial metastases.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Brain Neoplasms / drug therapy. Brain Neoplasms / secondary. Carcinoma, Non-Small-Cell Lung / secondary. Lung Neoplasms / pathology. Quinazolines / administration & dosage
  • [MeSH-minor] Adult. Aged. Dose-Response Relationship, Drug. Drug Administration Schedule. Female. Humans. Magnetic Resonance Imaging. Male. Middle Aged. Neoplasm Staging. Protein Kinase Inhibitors / administration & dosage. Risk Assessment. Survival Analysis. Treatment Outcome


17. Campos SM, Berlin ST, Parker LM, Chen WY, Bunnell CA, Atkinson T, Lee J, Matulonis U, Hirsch MS, Harris L, Krasner CN: Phase I trial of liposomal doxorubicin and ZD1839 in patients with refractory gynecological malignancies or metastatic breast cancer. Int J Clin Oncol; 2010 Aug;15(4):390-8
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  • [Title] Phase I trial of liposomal doxorubicin and ZD1839 in patients with refractory gynecological malignancies or metastatic breast cancer.
  • Preclinical data noted that ZD1839 acts synergistically with chemotherapy.
  • METHODS: Dose-limiting toxicity (DLT) was defined within the first two cycles of treatment.
  • Serious adverse events (SAEs) included one patient with mental status changes believed secondary to disease progression and two central nervous system (CNS) bleeds believed to be unrelated to the combination of study agents.
  • The best response to therapy included four partial responses and 20 patients with stable disease.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Breast Neoplasms / drug therapy. Drug Resistance, Neoplasm. Genital Neoplasms, Female / drug therapy
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Boston. Doxorubicin / administration & dosage. Female. Humans. Maximum Tolerated Dose. Middle Aged. Neoplasm Staging. Quinazolines / administration & dosage. Salvage Therapy. Time Factors. Treatment Outcome

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  • (PMID = 20405155.001).
  • [ISSN] 1437-7772
  • [Journal-full-title] International journal of clinical oncology
  • [ISO-abbreviation] Int. J. Clin. Oncol.
  • [Language] eng
  • [Publication-type] Clinical Trial, Phase I; Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't
  • [Publication-country] Japan
  • [Chemical-registry-number] 0 / Quinazolines; 80168379AG / Doxorubicin; S65743JHBS / gefitinib
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18. Tomizawa D, Koh K, Hirayama M, Miyamura T, Hatanaka M, Saikawa Y, Ishii E: Outcome of recurrent or refractory acute lymphoblastic leukemia in infants with MLL gene rearrangements: A report from the Japan Infant Leukemia Study Group. Pediatr Blood Cancer; 2009 Jul;52(7):808-13
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  • [Title] Outcome of recurrent or refractory acute lymphoblastic leukemia in infants with MLL gene rearrangements: A report from the Japan Infant Leukemia Study Group.
  • BACKGROUND: Despite the poor outcome of recurrent or refractory acute lymphoblastic leukemia (ALL) in infants with MLL gene rearrangement, few studies have focused on this specific group.
  • We conducted a retrospective analysis of infants with recurrent or refractory ALL from two previous consecutive Japanese studies to clarify the characteristics and prognostic factors among these patients PROCEDURE: All recurrent or refractory ALL infants with MLL gene rearrangement (MLL-R) who were registered in two consecutive Japanese nation-wide multicentric trials (MLL96 and MLL98; between 1995 and 2001) were eligible for the study.
  • With median follow-up period of 5.5 years, the 5-year overall survival (OS) rate after the second-line treatment was 25.6% +/- 6.9%.
  • Young age (<3 months) and central nervous system involvement at initial diagnosis were associated with poor outcome; however, failure to achieve remission after salvage therapy was the sole independent poor prognostic factor in multivariate analysis (P = 0.01).
  • CONCLUSIONS: The prognosis of infants with recurrent or refractory MLL-R ALL is extremely poor despite alternative treatments including HSCT; therefore, it is necessary to develop novel treatment strategies.
  • [MeSH-major] Drug Resistance, Neoplasm. Myeloid-Lymphoid Leukemia Protein / genetics. Neoplasm Recurrence, Local / genetics. Neoplasm Recurrence, Local / therapy. Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics. Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy
  • [MeSH-minor] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Bone Marrow Transplantation. Combined Modality Therapy. Disease-Free Survival. Female. Gene Rearrangement. Hematopoietic Stem Cell Transplantation. Histone-Lysine N-Methyltransferase. Humans. Infant. Male. Peripheral Blood Stem Cell Transplantation. Prognosis. Remission Induction. Retrospective Studies. Salvage Therapy. Survival Rate. Transplantation Conditioning. Treatment Outcome

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  • [Copyright] (c) 2009 Wiley-Liss, Inc.
  • (PMID = 19229974.001).
  • [ISSN] 1545-5017
  • [Journal-full-title] Pediatric blood & cancer
  • [ISO-abbreviation] Pediatr Blood Cancer
  • [Language] eng
  • [Publication-type] Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / MLL protein, human; 149025-06-9 / Myeloid-Lymphoid Leukemia Protein; EC 2.1.1.43 / Histone-Lysine N-Methyltransferase
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19. Pels H, Schulz H, Manzke O, Hom E, Thall A, Engert A: Intraventricular and intravenous treatment of a patient with refractory primary CNS lymphoma using rituximab. J Neurooncol; 2002 Sep;59(3):213-6
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  • [Title] Intraventricular and intravenous treatment of a patient with refractory primary CNS lymphoma using rituximab.
  • The treatment of primary central nervous system lymphoma (PCNSL) with chemo- and radiotherapy is efficient in terms of tumor response.
  • However, time to tumor progression often is of short duration and leptomeningeal relapse is common.
  • After treatment with intravenous and intraventricular administration of the chimeric anti-CD20 monoclonal antibody rituximab, a total clearing of lymphoma cells in the cerebrospinal fluid (CSF) was achieved.
  • There was no change in the size of the parenchymal tumor mass but there was slight improvement of clinical symptoms after therapy.
  • Antibody levels in CSF were measured at 7 timepoints during and after the treatment period.
  • These data suggest that intraventicular treatment with rituximab is safe and feasible with a potential activity on leptomeningeal tumor manifestation.
  • [MeSH-major] Antibodies, Monoclonal / administration & dosage. Antineoplastic Agents / administration & dosage. Brain Neoplasms / drug therapy. Lymphoma, B-Cell / drug therapy
  • [MeSH-minor] Aged. Antibodies, Monoclonal, Murine-Derived. Antigens, CD20 / metabolism. Blood Circulation / immunology. Humans. Infusions, Intravenous. Injections, Intraventricular. Magnetic Resonance Imaging. Male. Neoplasm Recurrence, Local / drug therapy. Neoplasm Recurrence, Local / immunology. Remission Induction. Rituximab

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  • (PMID = 12241117.001).
  • [ISSN] 0167-594X
  • [Journal-full-title] Journal of neuro-oncology
  • [ISO-abbreviation] J. Neurooncol.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Murine-Derived; 0 / Antigens, CD20; 0 / Antineoplastic Agents; 4F4X42SYQ6 / Rituximab
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20. Enting RH, Demopoulos A, DeAngelis LM, Abrey LE: Salvage therapy for primary CNS lymphoma with a combination of rituximab and temozolomide. Neurology; 2004 Sep 14;63(5):901-3
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  • [Title] Salvage therapy for primary CNS lymphoma with a combination of rituximab and temozolomide.
  • The authors evaluated the efficacy of a combination of rituximab and temozolomide for recurrent or refractory primary CNS lymphoma (PCNSL).
  • This combination merits further study and provides a reasonable therapeutic alternative for older patients with progressive PCNSL.
  • [MeSH-major] Antibodies, Monoclonal / therapeutic use. Antineoplastic Agents, Alkylating / therapeutic use. Central Nervous System Neoplasms / therapy. Dacarbazine / analogs & derivatives. Dacarbazine / therapeutic use. Immunotherapy. Lymphoma, B-Cell / therapy. Salvage Therapy
  • [MeSH-minor] Aged. Antibodies, Monoclonal, Murine-Derived. Antigens, CD20 / immunology. Antigens, Neoplasm / immunology. Brain Neoplasms / drug therapy. Brain Neoplasms / immunology. Brain Neoplasms / therapy. Cohort Studies. Combined Modality Therapy. Disease-Free Survival. Drug Evaluation. Drug Resistance, Neoplasm. Eye Neoplasms / drug therapy. Eye Neoplasms / immunology. Eye Neoplasms / therapy. Female. Humans. Life Tables. Male. Methotrexate / pharmacology. Methotrexate / therapeutic use. Middle Aged. Neoplasm Recurrence, Local / drug therapy. Neoplasm Recurrence, Local / therapy. Remission Induction. Retrospective Studies. Rituximab. Survival Analysis. Treatment Outcome

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  • [CommentIn] Neurology. 2005 Mar 8;64(5):934; author reply 934 [15753455.001]
  • (PMID = 15365145.001).
  • [ISSN] 1526-632X
  • [Journal-full-title] Neurology
  • [ISO-abbreviation] Neurology
  • [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 / Antibodies, Monoclonal, Murine-Derived; 0 / Antigens, CD20; 0 / Antigens, Neoplasm; 0 / Antineoplastic Agents, Alkylating; 4F4X42SYQ6 / Rituximab; 7GR28W0FJI / Dacarbazine; 85622-93-1 / temozolomide; YL5FZ2Y5U1 / Methotrexate
  • [Number-of-references] 10
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21. Nagasubramanian R, Dolan ME: Temozolomide: realizing the promise and potential. Curr Opin Oncol; 2003 Nov;15(6):412-8
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  • Numerous clinical studies have demonstrated the activity of temozolomide against recurrent or refractory gliomas and noncentral nervous system malignancies.
  • In the last 2 years, studies have focused on exploring strategies to optimize the efficacy of temozolomide, including evaluating different temozolomide dosing schedules and combining temozolomide with other antineoplastic agents, radiation therapy, or drug resistance-modifying agents.
  • RECENT FINDINGS: A critical review of these studies suggests that temozolomide, as currently used, has limited efficacy in treating refractory malignant infiltrative brain tumors, and survival benefit is, at best, a few weeks longer than that with procarbazine.
  • There is enthusiasm about the activity of temozolomide in the treatment of recurrent low-grade gliomas and advanced malignant melanomas.
  • Studies of temozolomide combined with novel drug resistance-modifying agents will likely improve disease control while minimizing toxicities, leading to improved survival benefit.
  • Larger, randomized trials comparing temozolomide with standard therapy are needed to confirm the suggested benefit from temozolomide in malignant brain tumors.
  • Temozolomide will continue to be attractive as an agent in the treatment of brain tumors because of its desirable features and safety.
  • [MeSH-major] Antineoplastic Agents, Alkylating / therapeutic use. Dacarbazine / analogs & derivatives. Dacarbazine / therapeutic use
  • [MeSH-minor] Brain Neoplasms / drug therapy. Central Nervous System Neoplasms / drug therapy. Drug Administration Schedule. Drug Resistance, Neoplasm / drug effects. Glioma / drug therapy. Humans

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  • (PMID = 14624222.001).
  • [ISSN] 1040-8746
  • [Journal-full-title] Current opinion in oncology
  • [ISO-abbreviation] Curr Opin Oncol
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / CA81485
  • [Publication-type] Journal Article; Research Support, U.S. Gov't, P.H.S.; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents, Alkylating; 7GR28W0FJI / Dacarbazine; 85622-93-1 / temozolomide
  • [Number-of-references] 53
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22. Seif AE, Reilly AF, Rheingold SR: Intrathecal liposomal cytarabine in relapsed or refractory infant and pediatric leukemias: the Children's Hospital of Philadelphia experience and review of the literature. J Pediatr Hematol Oncol; 2010 Nov;32(8):e349-52
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  • [Title] Intrathecal liposomal cytarabine in relapsed or refractory infant and pediatric leukemias: the Children's Hospital of Philadelphia experience and review of the literature.
  • Intrathecal chemotherapy is integral to curing childhood leukemia; however, bioavailability is limited by the blood-brain barrier.
  • Recently FDA-approved, intrathecal liposomal cytarabine (ITlipAC) increases drug concentration over time with fewer invasive procedures.
  • We present a series of 4 children, including 2 infants, with relapsed central nervous system leukemia who went into remission using ITlipAC, with a review of the literature reporting ITlipAC use in children with relapsed leukemia.
  • Drug-attributable side effects were observed more frequently in children with preexisting neurologic conditions and with adult dosing.
  • [MeSH-major] Antimetabolites, Antineoplastic / administration & dosage. Cytarabine / administration & dosage. Leukemia / drug therapy
  • [MeSH-minor] Adolescent. Child. Child, Preschool. Drug Resistance, Neoplasm. Female. Humans. Infant. Injections, Spinal. Liposomes / administration & dosage. Male. Philadelphia. Recurrence

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  • (PMID = 20962675.001).
  • [ISSN] 1536-3678
  • [Journal-full-title] Journal of pediatric hematology/oncology
  • [ISO-abbreviation] J. Pediatr. Hematol. Oncol.
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antimetabolites, Antineoplastic; 0 / Liposomes; 04079A1RDZ / Cytarabine
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23. Shamash J, O'Doherty CA, Oliver RT, Kelsey S, Gupta RK, Gallagher CJ, Newland AC, Lister TA: Should high-dose chemotherapy be used to consolidate second or third line treatment in relapsing germ cell tumours? Acta Oncol; 2000;39(7):857-63
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  • [Title] Should high-dose chemotherapy be used to consolidate second or third line treatment in relapsing germ cell tumours?
  • Thirty consecutive patients with relapsing germ cell tumours (GCT) were treated with induction chemotherapy and high-dose chemotherapy consolidation (HDCT).
  • During 1995, paclitaxel was introduced into second line therapy with cisplatin and ifosfamide (TIP), with immediate consolidation using HDCT.
  • At the same time the carboplatin dosing calculation was changed and an area under the curve (AUC) formula rather than by mg/m2 was used to calculate this.
  • The main determinant of post-treatment renal dysfunction was pretreatment renal function rather than the AUC dose of carboplatin.
  • Only a raised LDH prior to induction or absolute refractory disease in response to induction chemotherapy predicted poor survival following HDCT.
  • In patients relapsing following HDCT, the outcome was poor with many patients relapsing in the central nervous system and other new sites of disease.
  • Further responses were seen to chemotherapy or radiotherapy but these were not sustained.
  • The failure to improve results when HDCT was used as second line rather than third line chemotherapy consolidation was disappointing and adds to further uncertainty of the role of this approach as far as timing and the ideal preparative regimen are concerned.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Neoplasm Recurrence, Local / drug therapy. Neoplasms, Germ Cell and Embryonal / drug therapy
  • [MeSH-minor] Adolescent. Adult. Aged. Area Under Curve. Carboplatin / administration & dosage. Carboplatin / pharmacokinetics. Cisplatin / administration & dosage. Disease-Free Survival. Dose-Response Relationship, Drug. Etoposide / administration & dosage. Female. Humans. Ifosfamide / administration & dosage. Male. Middle Aged. Paclitaxel / administration & dosage. Prognosis. Taxoids

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  • (PMID = 11145445.001).
  • [ISSN] 0284-186X
  • [Journal-full-title] Acta oncologica (Stockholm, Sweden)
  • [ISO-abbreviation] Acta Oncol
  • [Language] eng
  • [Publication-type] Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Norway
  • [Chemical-registry-number] 0 / Taxoids; 6PLQ3CP4P3 / Etoposide; BG3F62OND5 / Carboplatin; P88XT4IS4D / Paclitaxel; Q20Q21Q62J / Cisplatin; UM20QQM95Y / Ifosfamide; ICE protocol 1; TIP regimen
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24. LoConte NK, Thomas JP, Alberti D, Heideman J, Binger K, Marnocha R, Utecht K, Geiger P, Eickhoff J, Wilding G, Kolesar J: A phase I pharmacodynamic trial of bortezomib in combination with doxorubicin in patients with advanced cancer. Cancer Chemother Pharmacol; 2008 Dec;63(1):109-15
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  • In addition, one patient developed grade 3 central nervous system toxicity in cycle 2 (not a DLT).
  • One patient with hormone refractory prostate cancer had a partial response.
  • This combination may be of special interest in multiple myeloma, given the activity of both drugs in that disease.

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  • (PMID = 18322686.001).
  • [ISSN] 1432-0843
  • [Journal-full-title] Cancer chemotherapy and pharmacology
  • [ISO-abbreviation] Cancer Chemother. Pharmacol.
  • [Language] ENG
  • [Grant] United States / NCI NIH HHS / CA / K12 CA087718; United States / NCI NIH HHS / CA / U01 CA062491; United States / NCRR NIH HHS / RR / M01 RR03186
  • [Publication-type] Clinical Trial, Phase I; Journal Article; Research Support, N.I.H., Extramural
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / Boronic Acids; 0 / Neoplasm Proteins; 0 / Proteasome Inhibitors; 0 / Pyrazines; 69G8BD63PP / Bortezomib; 80168379AG / Doxorubicin
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25. Reni M, Ferreri AJ: Therapeutic management of refractory or relapsed primary central nervous system lymphomas. Ann Hematol; 2001;80 Suppl 3:B113-7
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  • [Title] Therapeutic management of refractory or relapsed primary central nervous system lymphomas.
  • Despite the high rate of complete remission achieved with first-line therapy, 10-15% of immunocompetent PCNSL patients are treatment refractory while 35-60% relapse and die of lymphoma within a few months.
  • In many cases, salvage therapy produces a second complete remission with consequent symptomatic and survival improvement.
  • Due to the heterogeneity of both first and second line therapies employed, the optimal schedule for salvage therapy can not be identified.
  • Nevertheless, some therapeutic guidelines could be suggested.
  • Some authors have been able to minimize the incidence of actinic toxicity by using chemotherapy alone at failure.
  • In patients that have relapsed after receiving high-dose methotrexate (HD-MTX), the same drug again has been successfully employed while HD-cytarabine has been the most widely used cytostatic.
  • Meningeal relapse can be treated with spinal cord irradiation, intrathecal and/or systemic chemotherapy.
  • Salvage therapy, beyond improving survival, constitutes the selection ground for testing active agents.
  • Intriguing preliminary results from small pilot studies are now available with topotecan, rituximab, temozolomide, PCV regimen and HD-chemotherapy supported by autologous or allogeneic peripheral blood stem cells transplantation.
  • Considering its positive effect on survival and the potential improvement in neurological symptoms and quality of life, salvage therapy seems to be a valuable treatment in PCNSL patients.
  • Finally, the inclusion of relapsing or progressive PCNSL patients into second-line prospective clinical trials for testing therapeutic agents should be strongly encouraged.
  • [MeSH-major] Central Nervous System Neoplasms / therapy. Lymphoma, Non-Hodgkin / therapy. Neoplasm Recurrence, Local / therapy. Salvage Therapy
  • [MeSH-minor] Antimetabolites, Antineoplastic / administration & dosage. Antimetabolites, Antineoplastic / therapeutic use. Antineoplastic Combined Chemotherapy Protocols / administration & dosage. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Clinical Trials as Topic. Combined Modality Therapy. Cranial Irradiation. Cyclophosphamide / administration & dosage. Doxorubicin / administration & dosage. Hematopoietic Stem Cell Transplantation. Humans. Injections, Spinal. Methotrexate / administration & dosage. Methotrexate / therapeutic use. Prednisone / administration & dosage. Prognosis. Remission Induction. Retrospective Studies. Treatment Outcome. Vincristine / administration & dosage

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  • (PMID = 11757691.001).
  • [ISSN] 0939-5555
  • [Journal-full-title] Annals of hematology
  • [ISO-abbreviation] Ann. Hematol.
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / Antimetabolites, Antineoplastic; 5J49Q6B70F / Vincristine; 80168379AG / Doxorubicin; 8N3DW7272P / Cyclophosphamide; VB0R961HZT / Prednisone; YL5FZ2Y5U1 / Methotrexate; CHOP protocol
  • [Number-of-references] 40
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26. Pfeifer H, Wassmann B, Hofmann WK, Komor M, Scheuring U, Brück P, Binckebanck A, Schleyer E, Gökbuget N, Wolff T, Lübbert M, Leimer L, Gschaidmeier H, Hoelzer D, Ottmann OG: Risk and prognosis of central nervous system leukemia in patients with Philadelphia chromosome-positive acute leukemias treated with imatinib mesylate. Clin Cancer Res; 2003 Oct 15;9(13):4674-81
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  • [Title] Risk and prognosis of central nervous system leukemia in patients with Philadelphia chromosome-positive acute leukemias treated with imatinib mesylate.
  • PURPOSE: In patients with acute leukemias, a lymphoid phenotype, the presence of a Philadelphia chromosome (Ph), and inadequate central nervous system (CNS)-directed prophylactic therapy are risk factors for CNS involvement.
  • STUDY DESIGN: We analyzed 107 consecutive patients with relapsed or refractory Ph(+) acute lymphoid leukemia (ALL; n = 65) or chronic myeloid leukemia blast crisis (n = 42) who were enrolled in successive Phase II trials of single-agent imatinib and who did not receive routine prophylactic intrathecal chemotherapy.
  • RESULTS: CNS leukemia developed in 13 of 107 patients (12%) and was associated primarily with a lymphoid or bilineage phenotype (12 of 78; 15%) and with imatinib refractory Ph(+) ALL (5 of 19; 26%).
  • In contrast, two of three patients with exclusively meningeal leukemia achieved prolonged molecular remissions with intrathecal chemotherapy, cranial irradiation, and continued imatinib.
  • The optimal type of CNS-directed treatment and the extent of protection afforded by prophylactic cranial irradiation remain to be defined.
  • [MeSH-major] Central Nervous System Neoplasms / diagnosis. Leukemia / diagnosis. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy. Piperazines / pharmacology. Pyrimidines / pharmacology
  • [MeSH-minor] Adolescent. Adult. Aged. Antineoplastic Agents / pharmacology. Benzamides. Chromatography, High Pressure Liquid. Clinical Trials as Topic. DNA Mutational Analysis. Female. Humans. Imatinib Mesylate. Male. Middle Aged. Neoplasm Metastasis. Phenotype. Prognosis. Risk. Risk Factors. Time Factors. Treatment Outcome

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  • (PMID = 14581336.001).
  • [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 / Antineoplastic Agents; 0 / Benzamides; 0 / Piperazines; 0 / Pyrimidines; 8A1O1M485B / Imatinib Mesylate
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27. Evens AM, Ziegler SL, Gupta R, Augustyniak C, Gordon LI, Mehta J: Sustained hematologic and central nervous system remission with single-agent denileukin diftitox in refractory adult T-cell leukemia/lymphoma. Clin Lymphoma Myeloma; 2007 Jul;7(7):472-4
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  • [Title] Sustained hematologic and central nervous system remission with single-agent denileukin diftitox in refractory adult T-cell leukemia/lymphoma.
  • Initial treatment often includes zidovudine/interferon (IFN)-based therapy, although disease remission is typically not complete or durable.
  • This study reports on a 55-year-old man with relapsed/refractory leukemic-phase ATLL including significant central nervous system (CNS) disease with resistance to previous zidovudine/IFN and arsenic trioxide/IFN treatment.
  • The patient experienced a rapid hematologic and CNS clinical response with single-agent denileukin diftitox therapy (18 microg/kg per day for 5 days).
  • He tolerated 8 cycles of denileukin diftitox therapy well and experienced a sustained complete hematologic and CNS remission.
  • Further study examining denileukin diftitox in patients with relapsed/refractory ATLL is warranted.
  • [MeSH-major] Bone Marrow Transplantation. Central Nervous System Neoplasms / therapy. Diphtheria Toxin / administration & dosage. Hematologic Neoplasms / therapy. Interleukin-2 / administration & dosage. Leukemia-Lymphoma, Adult T-Cell / therapy
  • [MeSH-minor] Antineoplastic Combined Chemotherapy Protocols / administration & dosage. Arsenicals / administration & dosage. Drug Resistance, Neoplasm / drug effects. Humans. Interferons / administration & dosage. Male. Middle Aged. Oxides / administration & dosage. Recombinant Fusion Proteins / administration & dosage. Recurrence. Remission Induction. Transplantation, Homologous. Zidovudine / administration & dosage

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  • (PMID = 17875237.001).
  • [ISSN] 1557-9190
  • [Journal-full-title] Clinical lymphoma & myeloma
  • [ISO-abbreviation] Clin Lymphoma Myeloma
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Arsenicals; 0 / Diphtheria Toxin; 0 / Interleukin-2; 0 / Oxides; 0 / Recombinant Fusion Proteins; 25E79B5CTM / denileukin diftitox; 4B9XT59T7S / Zidovudine; 9008-11-1 / Interferons; S7V92P67HO / arsenic trioxide
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28. Voloschin AD, Betensky R, Wen PY, Hochberg F, Batchelor T: Topotecan as salvage therapy for relapsed or refractory primary central nervous system lymphoma. J Neurooncol; 2008 Jan;86(2):211-5
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  • [Title] Topotecan as salvage therapy for relapsed or refractory primary central nervous system lymphoma.
  • Treatment for patients with refractory or relapsed primary CNS lymphoma (PCNSL) remains unsatisfactory.
  • In this study 15 patients with refractory or relapsed PCNSL were treated with intravenous topotecan (1.5 mg/m(2)) for five consecutive days during each 21-day cycle.
  • All 15 patients had measurable, contrast-enhancing tumor on cranial MRI at the time of relapse.
  • Three patients had stable disease at the end of topotecan treatment.
  • Six patients (40%) had progressive disease during treatment.
  • Six out of 15 patients had grade 3 neutropenia, while 5/15 patients had grade 4 neutropenia, and 13/15 patients received g-CSF at some point during treatment.
  • There were no deaths directly related to treatment toxicity.
  • Our study shows that topotecan, as a salvage therapy in patients with relapsed or refractory PCNSL, is associated with an overall response proportion of 40% and should be considered in patients who have failed prior methotrexate-based chemotherapy and/or whole brain irradiation.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Brain Neoplasms / drug therapy. Lymphoma, Non-Hodgkin / drug therapy. Neoplasm Recurrence, Local / drug therapy. Salvage Therapy. Topotecan / therapeutic use
  • [MeSH-minor] Adult. Aged. Disease-Free Survival. Enzyme Inhibitors / therapeutic use. Female. Humans. Male. Middle Aged. Prospective Studies. Treatment Outcome


29. Fischer L, Thiel E, Klasen HA, Kirchen H, Jahnke K, Korfel A: Response of relapsed or refractory primary central nervous system lymphoma (PCNSL) to topotecan. Neurology; 2004 May 25;62(10):1885-7
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  • [Title] Response of relapsed or refractory primary central nervous system lymphoma (PCNSL) to topotecan.
  • The authors treated 16 immunocompetent patients with refractory or relapsed primary CNS lymphoma with topotecan.
  • Fifteen patients had been pretreated with up to three chemotherapy regimens, three of them additionally with whole brain irradiation (WBI), and one with WBI alone.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Brain Neoplasms / drug therapy. Lymphoma, Non-Hodgkin / drug therapy. Salvage Therapy. Topotecan / therapeutic use
  • [MeSH-minor] Adrenal Cortex Hormones / administration & dosage. Adrenal Cortex Hormones / therapeutic use. Adult. Aged. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Combined Modality Therapy. Cranial Irradiation. Disease-Free Survival. Enzyme Inhibitors / therapeutic use. Female. Humans. Male. Middle Aged. Neoplasm Proteins / antagonists & inhibitors. Prospective Studies. Remission Induction. Topoisomerase I Inhibitors. Treatment Outcome

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  • (PMID = 15159503.001).
  • [ISSN] 1526-632X
  • [Journal-full-title] Neurology
  • [ISO-abbreviation] Neurology
  • [Language] eng
  • [Publication-type] Clinical Trial; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Adrenal Cortex Hormones; 0 / Antineoplastic Agents; 0 / Enzyme Inhibitors; 0 / Neoplasm Proteins; 0 / Topoisomerase I Inhibitors; 7M7YKX2N15 / Topotecan
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30. Kong LY, Gelbard A, Wei J, Reina-Ortiz C, Wang Y, Yang EC, Hailemichael Y, Fokt I, Jayakumar A, Qiao W, Fuller GN, Overwijk WW, Priebe W, Heimberger AB: Inhibition of p-STAT3 enhances IFN-alpha efficacy against metastatic melanoma in a murine model. Clin Cancer Res; 2010 May 1;16(9):2550-61
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  • PURPOSE: Melanoma is a common and deadly tumor that upon metastasis to the central nervous system has a median survival duration of <6 months.
  • EXPERIMENTAL DESIGN: Combinational therapy of STAT3 blockade agents with IFN-alpha was investigated in a metastatic and an established syngeneic intracerebral murine tumor model of melanoma.
  • At autopsy, it was noted that there was a decreased trend in mice with melanoma developing leptomeningeal disease treated with combinational therapy.
  • CONCLUSIONS: The immune modulatory effects of STAT3 blockade can enhance the therapeutic efficacy of IFN-alpha immunotherapy by enhancing both innate and adaptive cytotoxic T-cell activities.
  • This combination therapy has the potential in the treatment of metastatic melanoma that is typically refractory to this type of immune therapeutic approach.

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  • [Copyright] Copyright 2010 AACR.
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  • (PMID = 20388845.001).
  • [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 / R01 CA120813-03; United States / NCI NIH HHS / CA / R01 CA120813; United States / NIAID NIH HHS / AI / AI077225-02; United States / NCI NIH HHS / CA / CA120813-03; United States / PHS HHS / / A177225-01; United States / NCI NIH HHS / CA / P50 CA093459-01A1; United States / NCI NIH HHS / CA / P50 CA093459; United States / NIAID NIH HHS / AI / R44 AI077225-02
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Cyanoacrylates; 0 / Immunologic Factors; 0 / Interferon-alpha; 0 / Pyridines; 0 / STAT3 Transcription Factor; 0 / Stat3 protein, mouse; 0 / WP 1193
  • [Other-IDs] NLM/ NIHMS229872; NLM/ PMC2936966
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31. Bahng H, Lee JH, Ahn JH, Lee JH, Lee JS, Kim SH, Kim WK, Lee KH: Combination chemotherapy utilizing continuous infusion of intermediate-dose cytarabine for refractory or recurrent acute myeloid leukemia. Leuk Res; 2001 Mar;25(3):213-6
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  • [Title] Combination chemotherapy utilizing continuous infusion of intermediate-dose cytarabine for refractory or recurrent acute myeloid leukemia.
  • Between October 1991 and December 1998, 19 patients (12 males and 7 females) with refractory (six patients) or recurrent (13 patients) AML were treated with a combination chemotherapy of cytarabine given by continuous infusion over 24-h at a rate of 1 upward arrow g/m2 per day for 5 days along with idarubicin (12 upward arrow mg/m2 per day x 3) and etoposide (150 mg /m(2) per day x 3).
  • Myelosuppression associated with chemotherapy was severe.
  • Median recovery time to ANC over 500/microl was 28 days (range, 25--59).
  • No central nervous system (CNS) toxicity was observed.
  • Further studies are necessary to elucidate optimum dose and schedule of cytarabine in a setting of refractory or relapsed acute myeloid leukemia (AML).
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / administration & dosage. Cytarabine / administration & dosage. Leukemia, Myeloid / drug therapy
  • [MeSH-minor] Actuarial Analysis. Acute Disease. Adolescent. Adult. Drug Resistance, Neoplasm. Female. Humans. Infusions, Intravenous. Male. Middle Aged. Recurrence. Remission Induction. Salvage Therapy. Survival Rate. Treatment Outcome

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  • (PMID = 11226516.001).
  • [ISSN] 0145-2126
  • [Journal-full-title] Leukemia research
  • [ISO-abbreviation] Leuk. Res.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 04079A1RDZ / Cytarabine
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32. Yamanaka R: [Medical management of primary central nervous system lymphoma refractory or resistant to standard of care treatment]. Brain Nerve; 2009 Oct;61(10):1155-64
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  • [Title] [Medical management of primary central nervous system lymphoma refractory or resistant to standard of care treatment].
  • Primary central nervous system lymphoma (PCNSL) is a non-Hodgkin's lymphoma arising in the central nervous system.
  • Combined irradition and methotrexate-based chemotherapy is the standard of care treatment for PCNSL.
  • The median overall survival achieved with this therapy is 25 to 51 months.
  • Failure after first-line treatment has been reported in most patients with PCNSL.
  • Salvage therapy is known to improve outcome, and although many different treatment modes have been attempted the optimal treatment schedule remains to be determined.
  • This review analyses the efficacy of salvage therapy by focusing on data obtained from reports reporting on salvage therapy.
  • Well-designed, randomized trials will help clarify issues such as the best chemotherapy regimen for second-line treatment.
  • [MeSH-major] Antineoplastic Agents / administration & dosage. Central Nervous System Neoplasms / drug therapy. Central Nervous System Neoplasms / radiotherapy. Lymphoma / drug therapy. Lymphoma / radiotherapy. Methotrexate / administration & dosage. Salvage Therapy
  • [MeSH-minor] Antibodies, Monoclonal / administration & dosage. Antibodies, Monoclonal, Murine-Derived. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Combined Modality Therapy. Dacarbazine / administration & dosage. Dacarbazine / analogs & derivatives. Drug Discovery. Hematopoietic Stem Cell Transplantation. Humans. Neoplasm Recurrence, Local / drug therapy. Neoplasm Recurrence, Local / radiotherapy. Rituximab. Topotecan / administration & dosage

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  • (PMID = 19882942.001).
  • [ISSN] 1881-6096
  • [Journal-full-title] Brain and nerve = Shinkei kenkyū no shinpo
  • [ISO-abbreviation] Brain Nerve
  • [Language] jpn
  • [Publication-type] English Abstract; Journal Article; Review
  • [Publication-country] Japan
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Murine-Derived; 0 / Antineoplastic Agents; 0 / ibritumomab tiuxetan; 4F4X42SYQ6 / Rituximab; 7GR28W0FJI / Dacarbazine; 7M7YKX2N15 / Topotecan; 85622-93-1 / temozolomide; YL5FZ2Y5U1 / Methotrexate
  • [Number-of-references] 76
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33. Pui CH, Pei D, Sandlund JT, Ribeiro RC, Rubnitz JE, Raimondi SC, Onciu M, Campana D, Kun LE, Jeha S, Cheng C, Howard SC, Metzger ML, Bhojwani D, Downing JR, Evans WE, Relling MV: Long-term results of St Jude Total Therapy Studies 11, 12, 13A, 13B, and 14 for childhood acute lymphoblastic leukemia. Leukemia; 2010 Feb;24(2):371-82
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  • [Title] Long-term results of St Jude Total Therapy Studies 11, 12, 13A, 13B, and 14 for childhood acute lymphoblastic leukemia.
  • We analyzed the long-term outcome of 1011 patients treated in five successive clinical trials (Total Therapy Studies 11, 12, 13A, 13B, and 14) between 1984 and 1999.
  • Early intensive triple intrathecal therapy, together with more effective systemic therapy, including consolidation and reinduction treatment (Studies 13A and 13B) as well as dexamethasone (Study 13B), resulted in a very low rate of isolated central nervous system (CNS) relapse rate (<2%), despite the reduced use of cranial irradiation.
  • Factors consistently associated with treatment outcome were age, leukocyte count, immunophenotype, DNA index, and minimal residual disease level after remission induction treatment.
  • Owing to concerns about therapy-related secondary myeloid leukemia and brain tumors, in our current trials we reserve the use of etoposide for patients with refractory or relapsed leukemia undergoing hematopoietic stem cell transplantation, and cranial irradiation for those with CNS relapse.

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  • (PMID = 20010620.001).
  • [ISSN] 1476-5551
  • [Journal-full-title] Leukemia
  • [ISO-abbreviation] Leukemia
  • [Language] ENG
  • [Grant] United States / NCI NIH HHS / CA / R01 CA060419-13; United States / NIGMS NIH HHS / GM / U01 GM061393-06; United States / NIGMS NIH HHS / GM / U01 GM061393; United States / NCI NIH HHS / CA / R01 CA051001-15; United States / NCI NIH HHS / CA / R01 CA078224; United States / NCI NIH HHS / CA / R37 CA036401-19; United States / NCI NIH HHS / CA / R37 CA036401; United States / NCI NIH HHS / CA / CA36401; United States / NCI NIH HHS / CA / CA21765; United States / NCI NIH HHS / CA / CA78224; United States / NCI NIH HHS / CA / R01 CA060419; United States / NCI NIH HHS / CA / CA60419; United States / NIGMS NIH HHS / GM / GM61393; United States / NCI NIH HHS / CA / P30 CA021765; United States / NCI NIH HHS / CA / P30 CA021765-31; United States / NCI NIH HHS / CA / R01 CA078224-09; United States / NCI NIH HHS / CA / R01 CA051001; United States / NCI NIH HHS / CA / R01 CA036401; United States / NCI NIH HHS / CA / CA51001; United States / NCI NIH HHS / CA / U01 CA060419
  • [Publication-type] Clinical Trial; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Other-IDs] NLM/ NIHMS137362; NLM/ PMC2820159
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34. Baruchel S, Sharp JR, Bartels U, Hukin J, Odame I, Portwine C, Strother D, Fryer C, Halton J, Egorin MJ, Reis RM, Martinho O, Stempak D, Hawkins C, Gammon J, Bouffet E: A Canadian paediatric brain tumour consortium (CPBTC) phase II molecularly targeted study of imatinib in recurrent and refractory paediatric central nervous system tumours. Eur J Cancer; 2009 Sep;45(13):2352-9
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  • [Title] A Canadian paediatric brain tumour consortium (CPBTC) phase II molecularly targeted study of imatinib in recurrent and refractory paediatric central nervous system tumours.
  • PURPOSE: To evaluate the safety, efficacy and pharmacokinetics of imatinib in children with recurrent or refractory central nervous system (CNS) tumours expressing KIT and/or PDGFRA.
  • METHODS: Nineteen patients aged 2-18 years, with recurrent or refractory CNS tumours expressing either of the target receptors KIT and/or PDGFRA (by immunohistochemistry) were eligible.
  • Our results suggest a possible relationship between KIT expression and maintenance of SD with imatinib treatment; KIT immunopositivity was seen in only 58% (11/19) of study participants overall, but in 100% of patients with SD at 38 weeks.
  • [MeSH-major] Antineoplastic Agents / pharmacokinetics. Central Nervous System Neoplasms / metabolism. Piperazines / pharmacokinetics. Protein Kinase Inhibitors / pharmacokinetics. Proto-Oncogene Proteins c-kit / metabolism. Pyrimidines / pharmacokinetics. Receptor, Platelet-Derived Growth Factor alpha / metabolism
  • [MeSH-minor] Adolescent. Benzamides. Canada. Child. Child, Preschool. Drug Resistance, Neoplasm / genetics. Female. Humans. Imatinib Mesylate. Male. Neoplasm Recurrence, Local / drug therapy. Neoplasm Recurrence, Local / genetics

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  • [CommentIn] Eur J Cancer. 2009 Sep;45(13):2236-8 [19540747.001]
  • (PMID = 19505817.001).
  • [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
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Benzamides; 0 / Piperazines; 0 / Protein Kinase Inhibitors; 0 / Pyrimidines; 8A1O1M485B / Imatinib Mesylate; EC 2.7.10.1 / Proto-Oncogene Proteins c-kit; EC 2.7.10.1 / Receptor, Platelet-Derived Growth Factor alpha
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35. Chamberlain MC: Salvage chemotherapy for recurrent spinal cord ependymona. Cancer; 2002 Sep 1;95(5):997-1002
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Salvage chemotherapy for recurrent spinal cord ependymona.
  • BACKGROUND: Ependymomas are reported to constitute 4% of all primary central nervous system (CNS) malignancies in adults, 30% of which occur in the spinal cord.
  • METHODS: Ten patients (6 males and 4 females with a median age of 30 years) with recurrent SCE were treated with oral etoposide (50mg/m(2)/day given daily for 21 days followed by a 14-day break and then repeated constituted a cycle of therapy).
  • All patients had failed surgery and radiotherapy and four patients had failed one prior chemotherapy.
  • Contrast-enhanced magnetic resonance imaging of the spine was performed every 8 weeks after a cycle of etoposide and before the next cycle of chemotherapy was initiated.
  • RESULTS: Treatment-related complications included alopecia in 9 patients, nonbloody diarrhea in 6 patients, a baseline weight loss of > 10% in 5 patients, Grade (according to the National Cancer Institute Common Toxicity Scale) 3-4 neutropenia in 3 patients, Grade 3-4 thrombocytopenia in 3 patients, and Grade 3-4 anemia in 2 patients.
  • There were no treatment-related deaths reported.
  • CONCLUSIONS: Chronic oral etoposide appears to be well tolerated, has modest toxicity, and had apparent activity in the small cohort of adults in the current study with surgically and medically refractory, recurrent, intradural intramedullary SCE.
  • [MeSH-major] Antineoplastic Agents, Phytogenic / pharmacology. Ependymoma / drug therapy. Etoposide / pharmacology. Neoplasm Recurrence, Local / drug therapy. Spinal Cord Neoplasms / drug therapy
  • [MeSH-minor] Administration, Oral. Adult. Alopecia / chemically induced. Disease-Free Survival. Drug Administration Schedule. Female. Humans. Male. Middle Aged. Salvage Therapy. Thrombocytopenia / chemically induced. Treatment Outcome. Weight Loss

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  • [Copyright] Copyright 2002 American Cancer Society.
  • (PMID = 12209682.001).
  • [ISSN] 0008-543X
  • [Journal-full-title] Cancer
  • [ISO-abbreviation] Cancer
  • [Language] eng
  • [Publication-type] Clinical Trial; Clinical Trial, Phase II; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents, Phytogenic; 6PLQ3CP4P3 / Etoposide
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36. Fischer L, Thiel E, Klasen HA, Birkmann J, Jahnke K, Martus P, Korfel A: Prospective trial on topotecan salvage therapy in primary CNS lymphoma. Ann Oncol; 2006 Jul;17(7):1141-5
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Prospective trial on topotecan salvage therapy in primary CNS lymphoma.
  • BACKGROUND: Standard salvage therapy has not been established for recurrent primary central nervous system lymphoma (PCNSL).
  • We report the final results of a prospective study on topotecan chemotherapy in relapsed or refractory PCNSL.
  • Fourteen patients were refractory to the last therapy, and 13 relapsed after a median period of 6.0 months.
  • Pretreatment with up to four regimens included chemotherapy in 26 patients and whole brain irradiation in 14.
  • CONCLUSION: Topotecan as monotherapy is active in relapsed and refractory PCNSL with tolerable toxicity.

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  • (PMID = 16603598.001).
  • [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] Clinical Trial, Phase II; Journal Article; Multicenter Study
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 7M7YKX2N15 / Topotecan
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