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1. Mesía R, Palmero R, Cos M, Vilajosana E, Vázquez S: Rapid palliation of symptoms with platinum-based chemotherapy plus cetuximab in recurrent oral cancer: a case report. Head Neck Oncol; 2010;2:3
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  • [Title] Rapid palliation of symptoms with platinum-based chemotherapy plus cetuximab in recurrent oral cancer: a case report.
  • BACKGROUND: Symptom control is an important consideration in the choice of treatment for patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN).
  • Patients who demonstrate objective tumour responses to platinum-based chemotherapy are more likely to have symptom relief than those who do not have such responses.
  • A phase III trial (EXTREME) showed that adding the epidermal growth factor receptor (EGFR)-targeting IgG1 monoclonal antibody cetuximab to first-line platinum-based chemotherapy significantly prolongs progression-free and overall survival and increases response rate compared with platinum-based chemotherapy alone.
  • We report here the case of a 60-year old female with recurrent squamous cell carcinoma of the gum who had rapid palliation of symptoms and reduction of facial disease mass following treatment with a combination of carboplatin/5-fluorouracil (5-FU) and cetuximab.
  • CASE PRESENTATION: The patient was diagnosed with T4N0 M0 disease of the oral cavity in November 2006 and underwent surgery, with R0 resection, followed by adjuvant radiotherapy and concomitant cisplatin chemotherapy.
  • The patient received 4 21-day cycles of carboplatin (AUC 5), 5-FU (1,000 mg/m2/day for 4 days) and cetuximab (400 mg/m2 initial dose followed by subsequently weekly doses of 250 mg/m2), with continuation of cetuximab monotherapy at the end of this time, and pain relief with topical fentanyl and oral morphine.
  • After 7 days of treatment, pain had reduced to 2/10, with discontinuation of morphine after 4 days, and the facial mass had reduced to 70 mm.
  • After 2 cycles of treatment, the facial mass had decreased to 40 mm.
  • After 3 cycles of treatment, pain and facial oedema had resolved completely and a cervical computed tomography scan showed a marked reduction in tumour mass.
  • CONCLUSION: This case illustrates the rapid reduction of tumour mass and disease-associated pain and oedema that can be achieved with a combination of platinum-based chemotherapy and cetuximab in recurrent and/or metastatic SCCHN.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Carcinoma, Squamous Cell / drug therapy. Mouth Neoplasms / drug therapy. Neoplasm Recurrence, Local / drug therapy

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  • (PMID = 20181021.001).
  • [ISSN] 1758-3284
  • [Journal-full-title] Head & neck oncology
  • [ISO-abbreviation] Head Neck Oncol
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Humanized; BG3F62OND5 / Carboplatin; PQX0D8J21J / Cetuximab; U3P01618RT / Fluorouracil
  • [Other-IDs] NLM/ PMC2832769
  • [General-notes] NLM/ Original DateCompleted: 20100629
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2. Argiris A, Li Y, Forastiere A: Prognostic factors and long-term survivorship in patients with recurrent or metastatic carcinoma of the head and neck. Cancer; 2004 Nov 15;101(10):2222-9
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  • [Title] Prognostic factors and long-term survivorship in patients with recurrent or metastatic carcinoma of the head and neck.
  • BACKGROUND: The current study was conducted to identify prognostic factors and report the characteristics of long-term survivors in patients with recurrent or metastatic carcinoma of the head and neck who were treated with cisplatin-based combination chemotherapy in two randomized, Phase III trials conducted by the Eastern Oncology Cooperative Group (ECOG) (E1393 and E1395).
  • On multivariate analysis, the following were found to be independent unfavorable predictors of objective response: weight loss of > 5%, an ECOG performance status of 1 (vs. 0), residual disease at the primary tumor site, a primary tumor site other than the oropharynx, prior radiation therapy (RT) (P = 0.056), and well/moderate tumor cell differentiation (P = 0.067).
  • Independent unfavorable prognostic factors for OS were weight loss, an ECOG performance status of 1 (vs. 0), well/moderate tumor cell differentiation, a primary tumor in the oral cavity or hypopharynx, and prior RT.
  • The following were found to be independent unfavorable prognostic factors for time to disease progression: well/moderate tumor cell differentiation, a oral cavity or hypopharyngeal primary tumor, and prior RT.
  • Two-year survivors were more likely to have achieved an objective response to chemotherapy, have poor tumor cell differentiation, be white, have an ECOG performance status of 0, and have received no prior RT.
  • CONCLUSIONS: Clinical parameters and tumor cell differentiation appear to be strong pretreatment predictors of outcome in patients with carcinoma of the head and neck and should be considered in the design of future randomized trials.
  • A small percentage of patients with recurrent head and neck carcinoma can achieve long-term survival.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Head and Neck Neoplasms / drug therapy. Head and Neck Neoplasms / mortality
  • [MeSH-minor] Adult. Aged. Cisplatin / therapeutic use. Disease Progression. Female. Fluorouracil / therapeutic use. Humans. Male. Middle Aged. Paclitaxel / therapeutic use. Prognosis. Randomized Controlled Trials as Topic. Survival Analysis. Treatment Outcome

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  • [Copyright] (c) 2004 American Cancer Society
  • (PMID = 15452834.001).
  • [ISSN] 0008-543X
  • [Journal-full-title] Cancer
  • [ISO-abbreviation] Cancer
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] P88XT4IS4D / Paclitaxel; Q20Q21Q62J / Cisplatin; U3P01618RT / Fluorouracil
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3. Kostrzewa JP, Lancaster WP, Iseli TA, Desmond RA, Carroll WR, Rosenthal EL: Outcomes of salvage surgery with free flap reconstruction for recurrent oral and oropharyngeal cancer. Laryngoscope; 2010 Feb;120(2):267-72
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  • [Title] Outcomes of salvage surgery with free flap reconstruction for recurrent oral and oropharyngeal cancer.
  • OBJECTIVES/HYPOTHESIS: To evaluate outcomes of salvage surgery with free flap reconstruction for recurrent squamous cell carcinoma of the oropharynx and oral cavity with increased use of chemoradiotherapy.
  • METHODS: All patients undergoing salvage surgery with free flap reconstruction for oropharynx (n = 36) and oral cavity (n = 36) squamous cell carcinomas between January 2001 and January 2008 were obtained.
  • RESULTS: Complications were more frequent in oropharynx than oral cavity tumors (36% and 14%, respectively; P = .05) requiring more secondary procedures (15 for oropharynx vs. six for oral cavity).
  • Median survival overall following salvage surgery was 44.8 months for oral cavity and 53.8 months for oropharynx head and neck squamous cell carcinoma.
  • CONCLUSIONS: Salvage surgery with free flap reconstruction for recurrent oral and oropharyngeal tumors after chemoradiotherapy has acceptable morbidity and similar cure rates as salvage following radiotherapy without chemotherapy.

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  • (PMID = 20013840.001).
  • [ISSN] 1531-4995
  • [Journal-full-title] The Laryngoscope
  • [ISO-abbreviation] Laryngoscope
  • [Language] ENG
  • [Grant] United States / NCI NIH HHS / CA / R01 CA142637; None / None / / R01 CA142637-02; United States / NCI NIH HHS / CA / R01 CA142637-02
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Other-IDs] NLM/ NIHMS258253; NLM/ PMC3389788
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4. Galetta D, Giotta F, Rosati G, Gebbia V, Manzione L, Di Bisceglie M, Borsellino N, Colucci G: Carboplatin in combination with raltitrexed in recurrent and metastatic head and neck squamous cell carcinoma: A multicentre phase II study of the Gruppo Oncologico Dell'Italia Meridionale (G.O.I.M.). Anticancer Res; 2005 Nov-Dec;25(6C):4445-9
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  • [Title] Carboplatin in combination with raltitrexed in recurrent and metastatic head and neck squamous cell carcinoma: A multicentre phase II study of the Gruppo Oncologico Dell'Italia Meridionale (G.O.I.M.).
  • BACKGROUND: The combination of cisplatin (CDDP) and 5-Fluorouracil (5-FU) is a standard regimen for the treatment of recurrent and metastatic head and neck squamous cell carcinoma (HNSCC).
  • This combination shows a relevant toxicity and new chemotherapy associations with a more favourable toxicity profile are awaited.
  • Raltitrexed (R) is a potent and specific thymidylate synthase inhibitor with activity comparable to that of 5-FU in colorectal cancer; moreover, it showed activity as a single agent in HNSCC.
  • MATERIALS AND METHODS: Since 2001, a multicentre, phase II trial has been underway to evaluate the efficacy and toxicity of the CB+R combination in untreated patients with recurrent or metastatic HNSCC.
  • Patients had a histo/cytologically proven recurrent or metastatic HNSCC; patients with locally advanced disease not amenable to CDDP+5-FU treatment were also included.
  • Twelve patients were staged III and 20 were metastatic (10 recurrent).
  • The oral cavity/oropharynx were the primary site in 20 patients and the larynx in 10 patients.
  • The median time to progression was 4.2 months and median duration of survival was 9.8 months.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Carcinoma, Squamous Cell / drug therapy. Head and Neck Neoplasms / drug therapy. Neoplasm Recurrence, Local / drug therapy

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  • (PMID = 16334124.001).
  • [ISSN] 0250-7005
  • [Journal-full-title] Anticancer research
  • [ISO-abbreviation] Anticancer Res.
  • [Language] eng
  • [Publication-type] Clinical Trial, Phase II; Journal Article; Multicenter Study
  • [Publication-country] Greece
  • [Chemical-registry-number] 0 / Quinazolines; 0 / Thiophenes; BG3F62OND5 / Carboplatin; FCB9EGG971 / raltitrexed
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5. Sudbø J, Lippman SM, Lee JJ, Mao L, Kildal W, Sudbø A, Sagen S, Bryne M, El-Naggar A, Risberg B, Evensen JF, Reith A: The influence of resection and aneuploidy on mortality in oral leukoplakia. N Engl J Med; 2004 Apr 1;350(14):1405-13
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  • [Title] The influence of resection and aneuploidy on mortality in oral leukoplakia.
  • BACKGROUND: Although the standard treatment of oral leukoplakia ranges from watchful waiting to complete resection, the value of these approaches is unknown.
  • METHODS: We studied the relations among resection, ploidy status, and death from cancer in 103 patients with diploid dysplastic oral leukoplakia, 20 patients with tetraploid lesions, and 27 patients with aneuploid lesions.
  • Data on cancer-specific mortality and treatment were obtained from the Cancer Registry of Norway, Statistics Norway, and chart reviews.
  • RESULTS: Primary oral carcinoma developed in 47 of the 150 patients with leukoplakia (31 percent)--5 with diploid, 16 with tetraploid, and 26 with aneuploid leukoplakia--during a mean follow-up of 80 months (range, 4 to 237).
  • The margin status of the initial leukoplakia resection had no relation to the development of oral cancer (P=0.95).
  • Twenty-six of the 47 patients in whom cancer developed (4 with prior tetraploid and 22 with prior aneuploid lesions) had recurrences (55 percent); the recurrences were more frequently multiple and distant (within the oral cavity) among patients with aneuploid lesions than among those with tetraploid or diploid lesions.
  • All 47 patients underwent a standard regimen of surgery and radiation, followed by chemotherapy in the 26 with recurrent cancer.
  • Only patients with aneuploid leukoplakia died of oral cancer; the five-year rate of death from cancer was 72 percent.
  • CONCLUSIONS: Complete resection of aneuploid leukoplakia does not reduce the high risk of aggressive carcinoma and death from oral cancer.
  • [MeSH-major] Aneuploidy. Leukoplakia, Oral / genetics. Leukoplakia, Oral / surgery. Mouth Neoplasms / mortality
  • [MeSH-minor] Aged. Combined Modality Therapy. DNA, Neoplasm. Female. Follow-Up Studies. Humans. Male. Middle Aged. Neoplasm Recurrence, Local / therapy. Neoplasm Staging. Prognosis. Survival Analysis

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  • [Copyright] Copyright 2004 Massachusetts Medical Society
  • [CommentIn] N Engl J Med. 2006 Feb 9;354(6):638 [16428677.001]
  • [CommentIn] N Engl J Med. 2004 Apr 1;350(14):1382-4 [15070786.001]
  • [CommentIn] N Engl J Med. 2004 Jun 24;350(26):2718-9; author reply 2718-9 [15215492.001]
  • [CommentIn] N Engl J Med. 2004 Jun 24;350(26):2718-9; author reply 2718-9 [15218579.001]
  • [RetractionIn] Curfman GD, Morrissey S, Drazen JM. N Engl J Med. 2006 Nov 2;355(18):1927 [17079770.001]
  • (PMID = 15070790.001).
  • [ISSN] 1533-4406
  • [Journal-full-title] The New England journal of medicine
  • [ISO-abbreviation] N. Engl. J. Med.
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / CA16672
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.; Retracted Publication
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / DNA, Neoplasm
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6. Sagowski C, Kehrl W, Hegewisch-Becker S, Wenzel S, Jaehne M, Panse J, Nierhaus A: [Tumor oxygenation in combined whole body hyperthermia and polychemotherapy. Studies exemplified by recurrent carcinoma of the mouth cavity]. HNO; 2000 Dec;48(12):949-54
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  • [Title] [Tumor oxygenation in combined whole body hyperthermia and polychemotherapy. Studies exemplified by recurrent carcinoma of the mouth cavity].
  • BACKGROUND AND OBJECTIVE: Previous studies have reported synergistic effects of combined hyperthermia and chemotherapy and/or irradiation.
  • The response to irradiation and chemotherapy of well-oxygenated and vascularized tumors generally is better than that of hypoxic tumors.
  • Therefore, tumor oxygenation is recognized as an important predictive factor in the therapy of malignant tumors.
  • PATIENTS/METHODS: Whole-body hyperthermia, as heat radiation (Enthermics Medical Systems RHS-7500), was applied to the narcotised 60-year-old male patient with a local recurrence tumor pT3 pN2b M0 squamous cell carcinoma of the oral cavity.
  • Tumor oxygenation and temperature were measured by LICOX catheters via one-point measurement during the entire hyperthermia treatment (3.5 h).
  • Parallelly, chemotherapy (ifosfamide/Carboplatin) was given in four cycles (one cycle/month).
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Carcinoma, Squamous Cell / blood supply. Cell Hypoxia / physiology. Hyperthermia, Induced / instrumentation. Mouth Neoplasms / blood supply. Neoplasm Recurrence, Local / blood supply
  • [MeSH-minor] Combined Modality Therapy. Humans. Male. Middle Aged. Neoplasm Staging

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  • (PMID = 11196098.001).
  • [ISSN] 0017-6192
  • [Journal-full-title] HNO
  • [ISO-abbreviation] HNO
  • [Language] ger
  • [Publication-type] Case Reports; English Abstract; Journal Article
  • [Publication-country] Germany
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7. Sagowski C, Jaehne M, Kehrl W, Hegewisch-Becker S, Wenzel S, Panse J, Nierhaus A: Tumor oxygenation under combined whole-body-hyperthermia and polychemotherapy in a case of recurrent carcinoma of the oral cavity. Eur Arch Otorhinolaryngol; 2002 Jan;259(1):27-31
Hazardous Substances Data Bank. OXYGEN .

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Tumor oxygenation under combined whole-body-hyperthermia and polychemotherapy in a case of recurrent carcinoma of the oral cavity.
  • BACKGROUND: Previous studies have reported synergistic effects of combined hyperthermia and chemotherapy and/or irradiation.
  • Tumor response to irradiation and chemotherapy of well-oxygenated and vascularized tumors, in general, is superior to that of hypoxic tumors.
  • Therefore, tumor oxygenation is recognized as an important predictive factor in the therapy of malignant tumors.
  • Technically, the head-neck area remains outside the hyperthermia chamber during whole-body hyperthermia (WBH) as currently applied in a number of cancer treatment regimens.
  • The aim of this therapeutic approach was to evaluate whether the blood flow during WBH also increased in the head-neck region and, if so, whether tumor oxygenation increase accordingly.
  • METHODS: A 60-year-old male Caucasian patient, with the original diagnosis of pT3 pN2b M0 squamous cell carcinoma of the oral cavity, who had undergone primary surgery and irradiation (total dose 60 Gy), developed three local recurrences with consecutive surgical resection, presenting now with another recurrent local tumor (histologically confirmed) without surgical or radiotherapeutical options due to lymphangiosis carcinomatosa.
  • WBH was applied under full anaesthesia, using a humidified radiant heat device (Enthermics Medical Systems RHS-7500) in combination with synchronous application of chemotherapy (ifosfamide and carboplatin).
  • Four cycles of this combined treatment (one cycle per month) were given.
  • Tumor oxygenation and temperature were continuously monitored by Licox catheters by means of one point measurement during each treatment (3.5 h).
  • RESULTS: With a latency of 10 min, the increase of intratumoral temperature in the oral cavity was comparable to reference values in the esophagous.
  • Maximum intratumoral temperature (oral cavity) was 41.8 degrees C (F).
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Carcinoma, Squamous Cell / therapy. Hyperthermia, Induced. Mouth Neoplasms / therapy. Oxygen / metabolism
  • [MeSH-minor] Combined Modality Therapy. Humans. Male. Middle Aged. Neoplasm Recurrence, Local. Partial Pressure

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  • (PMID = 11954922.001).
  • [ISSN] 0937-4477
  • [Journal-full-title] European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery
  • [ISO-abbreviation] Eur Arch Otorhinolaryngol
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Germany
  • [Chemical-registry-number] S88TT14065 / Oxygen
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8. Ariyoshi Y, Miyatake S, Kimura Y, Shimahara T, Kawabata S, Nagata K, Suzuki M, Maruhashi A, Ono K, Shimahara M: Boron neuron capture therapy using epithermal neutrons for recurrent cancer in the oral cavity and cervical lymph node metastasis. Oncol Rep; 2007 Oct;18(4):861-6
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  • [Title] Boron neuron capture therapy using epithermal neutrons for recurrent cancer in the oral cavity and cervical lymph node metastasis.
  • The purpose of this clinical trial was to evaluate the utility of boron neutron capture therapy (BNCT) using epithermal neutrons for cases of recurrent cancer in the oral cavity, which are not indicated for a conventional treatment modality.
  • We enrolled four patients with local recurrence or metastasis to the regional lymph nodes after completion of initial treatments, including surgery, chemotherapy and radiotherapy.
  • Before receiving BNCT, patients underwent 18F-p-bononophenylalanine (BPA) positron emission tomography (PET) examinations to assess the BPA accumulation ratios in tumors and normal tissues.
  • Before BNCT, that patient could not be discharged from the hospital because of eating difficulties and malaise; after treatment, he was comfortably discharged.
  • Mild malaise, oral mucositis and alopecia were seen as mild adverse effects; however, no life-threatening systemic symptoms were observed in any of the cases.
  • Our results suggested that BNCT is a useful treatment modality for recurrent or regionally metastasized oral cancer.
  • [MeSH-major] Boron Neutron Capture Therapy / methods. Mouth Neoplasms / radiotherapy. Neoplasm Recurrence, Local / radiotherapy. Neutrons
  • [MeSH-minor] Adenocarcinoma / radiotherapy. Adult. Aged. Boron Compounds / therapeutic use. Carcinoma, Mucoepidermoid / radiotherapy. Carcinoma, Squamous Cell / radiotherapy. Female. Head and Neck Neoplasms / radiotherapy. Humans. Lymphatic Metastasis / radiotherapy. Magnetic Resonance Imaging. Male. Middle Aged. Positron-Emission Tomography. Tomography, X-Ray Computed. Treatment Outcome

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  • (PMID = 17786347.001).
  • [ISSN] 1021-335X
  • [Journal-full-title] Oncology reports
  • [ISO-abbreviation] Oncol. Rep.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Greece
  • [Chemical-registry-number] 0 / Boron Compounds
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9. Kovács AF, Eberlein K, Hülsmann T: Organ preservation treatment using TPF-a pilot study in patients with advanced primary and recurrent cancer of the oral cavity and the maxillary sinus. Oral Maxillofac Surg; 2009 Jun;13(2):87-93
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  • [Title] Organ preservation treatment using TPF-a pilot study in patients with advanced primary and recurrent cancer of the oral cavity and the maxillary sinus.
  • PURPOSE: Induction chemotherapy with Taxotere, cisplatin, and 5-fluororacil (TPF) was mainly used in hypopharyngeal and laryngeal cancer patients for larynx preservation.
  • This study aimed to assess feasibility and toxicity in oral cavity and maxillary sinus cancer patients.
  • PATIENTS AND METHODS: Between 2003 and 2008, 21 patients (18 male, three female; mean age 58 years; 15 patients Eastern Cooperative Oncology Group > or =1) suffering from advanced squamous cell cancers of the oral cavity (seven primaries, eight locoregional recurrences) and the maxillary sinus (six patients) were prospectively treated with three cycles of TPF (q3w) and were scheduled to undergo definitive chemoradiation.
  • Reasons for incomplete treatment were tumor progression, edema, seizure, bad general condition, sepsis, pneumonia (each once).
  • The infections led to two treatment-related deaths (9.5%).
  • Ten patients underwent a definitive chemoradiation or radiation (47.6%).
  • After a mean observation time of 17 months, nine patients are alive; one of them developed a local recurrence.
  • CONCLUSIONS: Chemotherapy with TPF is a highly effective treatment with considerable toxicity that needs special expertise which is best assured in a multidisciplinary setting.
  • Pretreated recurrent cancers demonstrated bad response.
  • A target for organ preservation could be the maxillary sinus; due to tumor regression in advanced oral tongue cancer, consecutively, a reduced function has to be encountered.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Carcinoma, Squamous Cell / drug therapy. Maxillary Sinus Neoplasms / drug therapy. Mouth Neoplasms / drug therapy. Neoplasm Recurrence, Local / drug therapy
  • [MeSH-minor] Aged. Antimetabolites, Antineoplastic / administration & dosage. Antimetabolites, Antineoplastic / adverse effects. Antineoplastic Agents / administration & dosage. Antineoplastic Agents / adverse effects. Cisplatin / administration & dosage. Cisplatin / adverse effects. Cisplatin / therapeutic use. Disease Progression. Feasibility Studies. Female. Fluorouracil / administration & dosage. Fluorouracil / adverse effects. Fluorouracil / therapeutic use. Follow-Up Studies. Humans. Leukopenia / chemically induced. Male. Middle Aged. Neoplasm Staging. Neutropenia / chemically induced. Opportunistic Infections / etiology. Pilot Projects. Prospective Studies. Radiotherapy, Adjuvant. Remission Induction. Stomatitis / chemically induced. Survival Rate. Taxoids / administration & dosage. Taxoids / adverse effects. Taxoids / therapeutic use

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  • (PMID = 19430823.001).
  • [ISSN] 1865-1550
  • [Journal-full-title] Oral and maxillofacial surgery
  • [ISO-abbreviation] Oral Maxillofac Surg
  • [Language] eng
  • [Publication-type] Clinical Trial; Journal Article
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / Antimetabolites, Antineoplastic; 0 / Antineoplastic Agents; 0 / Taxoids; Q20Q21Q62J / Cisplatin; U3P01618RT / Fluorouracil; TPF protocol
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10. Massa E, Dessì M, Gaspardini G, Saba F, Cherchi V, Mantovani G: Phase II study of vinorelbine/cetuximab in patients with recurrent/metastatic squamous cell carcinoma of the head and neck progressing after at least two chemotherapy regimens. Oral Oncol; 2010 Nov;46(11):818-21
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  • [Title] Phase II study of vinorelbine/cetuximab in patients with recurrent/metastatic squamous cell carcinoma of the head and neck progressing after at least two chemotherapy regimens.
  • The aim of the present study was to identify a potentially effective new treatment regimen for patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck in disease progression after at least two previous chemotherapy regimens.
  • The regimen was administered to patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck previously treated with surgery, radiotherapy or both and progressing after at least two chemotherapy regimens.
  • Twenty-four patients with histologically confirmed tumors of oral cavity, oropharynx, hypopharynx and larynx were enrolled.
  • After 3 cycles of treatment 23 patients (95.8%) were evaluable for response: 4 patients had partial response; 12 stable disease and 7 progressive disease.
  • The present study shows that the combination of Vinorelbine and Cetuximab in recurrent and/or metastatic squamous cell carcinoma of the head and neck patients is effective, feasible and has a good safety profile.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / administration & dosage. Carcinoma, Squamous Cell / drug therapy. Head and Neck Neoplasms / drug therapy. Neoplasm Recurrence, Local / drug therapy

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  • [Copyright] Copyright © 2010 Elsevier Ltd. All rights reserved.
  • (PMID = 20920877.001).
  • [ISSN] 1879-0593
  • [Journal-full-title] Oral oncology
  • [ISO-abbreviation] Oral Oncol.
  • [Language] eng
  • [Publication-type] Clinical Trial, Phase II; Journal Article; Multicenter Study
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Humanized; 5V9KLZ54CY / Vinblastine; PQX0D8J21J / Cetuximab; Q20Q21Q62J / Cisplatin; Q6C979R91Y / vinorelbine
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11. Schwartz GJ, Mehta RH, Wenig BL, Shaligram C, Portugal LG: Salvage treatment for recurrent squamous cell carcinoma of the oral cavity. Head Neck; 2000 Jan;22(1):34-41
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  • [Title] Salvage treatment for recurrent squamous cell carcinoma of the oral cavity.
  • BACKGROUND: Squamous cell carcinoma (SCCA) of the oral cavity recurs with a frequency of 25%-48%, a fact that usually portends a poor prognosis.
  • Investigators have also claimed that restaging recurrent tumors provides useful prognostic information, although this has not been demonstrated with tumors of the oral cavity.
  • (1) to report the patterns of recurrent SCCA of the oral cavity;.
  • (2) to examine the benefit of restaging oral cavity tumors, and (3) to compare different treatment modalities in the management of recurrent SCCA of the oral cavity.
  • Materials and Methods Thirty-eight patients who developed recurrent SCCA of the oral cavity were reviewed.
  • Salvage treatment consisted of surgery, chemotherapy, radiation therapy, or a combination of these modalities.
  • Survival analysis was based on the stage of the primary and recurrent tumors and the type of salvage treatment received.
  • Patients who recurred more than 6 months after completion of their primary treatment had improved survival compared with those who recurred within 6 months of initial treatment.
  • Individuals with stage I-II primary tumors had significantly improved salvage time and total survival time compared with those with stage III-IV primary tumors (p < 0.005 and p < 0.001).
  • Conversely, the stage of the recurrent tumor was not predictive of either improved salvage time or total survival time.
  • Patients who underwent salvage surgery had significantly improved salvage time and total survival time compared with those who received chemotherapy and/or radiation therapy (p < 0.001 and p < 0.002).
  • Neither the stage of the primary or recurrent tumors nor the type of salvage treatment received significantly correlated with an improved cure rate.
  • CONCLUSIONS: Squamous cell carcinoma of the oral cavity is most likely to recur at the primary site.
  • The stage of the primary tumor is significantly correlated with survival even after recurrence, but the stage of the recurrent tumor is not significantly correlated with survival.
  • Patients most likely to benefit from retreatment are those who (1) have primary tumors stage I-II, (2) recur greater than 6 months after their initial treatment, and (3) develop recurrences that are amenable to salvage surgery.
  • [MeSH-major] Carcinoma, Squamous Cell / therapy. Mouth Neoplasms / therapy. Neoplasm Recurrence, Local / therapy. Salvage Therapy
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Combined Modality Therapy. Evaluation Studies as Topic. Female. Humans. Male. Middle Aged. Neoplasm Staging. Prognosis. Registries. Survival Rate. Treatment Outcome


12. Agra IM, Carvalho AL, Ulbrich FS, de Campos OD, Martins EP, Magrin J, Kowalski LP: Prognostic factors in salvage surgery for recurrent oral and oropharyngeal cancer. Head Neck; 2006 Feb;28(2):107-13
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  • [Title] Prognostic factors in salvage surgery for recurrent oral and oropharyngeal cancer.
  • BACKGROUND: Therapeutic decisions in recurrent oral and oropharyngeal squamous carcinoma (SCC) remain controversial.
  • METHODS: Two hundred forty-six consecutive patients who underwent salvage surgery for recurrent squamous cell carcinoma (SCC) of the oral cavity and oropharynx were studied.
  • The tumor sites were lip, 33 cases; oral cavity, 143; oropharynx, 70.
  • The previous treatment was surgery in 73 patients, radiotherapy in 96, combined surgery and radiotherapy in 76, and chemotherapy in one.
  • CONCLUSION: Patients with recurrent oral and oropharyngeal SCC at initial clinical stages (rCS I and II) and with a DFI greater than 1 year had a favorable prognosis.
  • [MeSH-major] Carcinoma, Squamous Cell / surgery. Mouth Neoplasms / surgery. Neoplasm Recurrence, Local / surgery. Oropharyngeal Neoplasms / surgery. Salvage Therapy

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  • [Copyright] Copyright 2005 Wiley Periodicals, Inc.
  • (PMID = 16388526.001).
  • [ISSN] 1043-3074
  • [Journal-full-title] Head & neck
  • [ISO-abbreviation] Head Neck
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
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13. Diaz de Corcuera I, Serrano C, Pérez J, Quispe I, Arguis M, Muñoz E, Benavente S, Martínez P, Parera M, Del Campo JM: Weekly cetuximab and paclitaxel combination in metastatic/recurrent squamous cell cancer carcinoma of the head and neck (SCCHN): Clinical experience of a single institution. J Clin Oncol; 2009 May 20;27(15_suppl):e17043

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Weekly cetuximab and paclitaxel combination in metastatic/recurrent squamous cell cancer carcinoma of the head and neck (SCCHN): Clinical experience of a single institution.
  • : e17043 Background: Results of a recent phase III randomized study with cetuximab and platin-5FU chemotherapy support its use in recurrent/metastatic SCCHN.
  • METHODS: From our database, we conducted a retrospective study of 20 patients with recurrent SCCHN who did not meet criteria for platin therapy and were treated with weekly P (80 mg/m2) and C (initially 400 mg/m2 followed by 250 mg/m2) until progression or intolerable toxicity.
  • We have collected data regarding previous treatments, response rate (RR), progression free survival (PFS), overall survival (OS) and toxicity.
  • Oral cavity (35%) and oropharynx (25%) were the most frequent locations.
  • Most of the pts (13/20) had been treated with previous chemotherapy combinations (range 1-3 lines).
  • CONCLUSIONS: Our analysis confirms that weekly paclitaxel-cetuximab is an effective and safety combination in metastatic/recurrent SCCHN.
  • Treatment is very well tolerated and could be a good alternative to platin-based chemotherapy in unfit patients for this therapy.

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  • (PMID = 27961779.001).
  • [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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14. Langer CJ, Harris J, Horwitz E, Nicolaou N, Kies M, Curran W, Wong S, Ang KK: Phase II trial of concurrent split course hyperfractionated radiotherapy (Hfx RT), cisplatin (DDP) and paclitaxel (P) in patients with recurrent, previously irradiated squamous cell carcinoma of the head and neck (SCCHN): Results of RTOG 9911. J Clin Oncol; 2004 Jul 15;22(14_suppl):5509

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Phase II trial of concurrent split course hyperfractionated radiotherapy (Hfx RT), cisplatin (DDP) and paclitaxel (P) in patients with recurrent, previously irradiated squamous cell carcinoma of the head and neck (SCCHN): Results of RTOG 9911.
  • : 5509 Background: Recurrent SCCHN, if not curable by surgery or RT, is almost always fatal.
  • Chemotherapy (CTx) alone (eg.
  • DDP, 5FU) yields median survival times (MST) of 8-10 mos and 1 yr survival (OS) of ≤ 35% at best.
  • METHODS: Eligibility stipulated recurrent SCCHN or second 1° tumors (SPT) in a previous RT field; measurable tumor; ≥ 75% of tumor volume previously treated to 45 Gy-75 Gy; ≥ 6 mos elapsed from prior RT, ECOG PS 0-1; ANC ≥1500, plts ≥ 100K, bili ≤1.5 mg/dl, creat ≤ 1.5 mg/dl, and absence of distant mets.
  • Pts received HFx RT (1.5 Gy/Fx BID x 5d every 2 wks x 4), in combination with DDP 15 mg/m<sup>2</sup> IV QD x 5 and P 20 mg/m<sup>2</sup> IV QD x 5 q 2 wks x 4.
  • 22% had SPTs. Oropharynx (37%) and oral cavity (32%) were the predominant 1° sites.
  • Median prior RT dose was 65.4 Gy (range, 45-73 Gy).
  • CONCLUSIONS: Despite a fairly high inc. of Gr 5 tox, 1- and 2-yr OS rates for split course HFxRT/DDP/P exceed results generally seen with chemotherapy alone.

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  • (PMID = 28014195.001).
  • [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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15. Berrocal A, Pastor M, Caballero C, Segura A, Garcera S, Oltra A, Nogueron E, Blasco A, Lopez P, Camps C: Phase II study of paclitaxel, tegafur/uracil and folinic acid as first line treatment in metastatic or recurrent head and neck squamous cell carcinomas. J Clin Oncol; 2004 Jul 15;22(14_suppl):5581

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Phase II study of paclitaxel, tegafur/uracil and folinic acid as first line treatment in metastatic or recurrent head and neck squamous cell carcinomas.
  • : 5581 Background: Cisplatin alone or in combination remains the standard for recurrent/metastatic head and neck carcinoma, however it is associated with significant toxicity.
  • METHODS: Recurrent and/or metastatic squamous head and neck carcinoma patients not previously chemotherapy treated.
  • Primary tumours localizations were larinx / paranasal sinus / oral cavity / oropharinx / hipopharinx / others 12/1/4/4/2/6.

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  • (PMID = 28014070.001).
  • [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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16. Martínez-Monge R, Gómez-Iturriaga A, Cambeiro M, Garrán C, Montesdeoca N, Aristu JJ, Alcalde J: Phase I-II trial of perioperative high-dose-rate brachytherapy in oral cavity and oropharyngeal cancer. Brachytherapy; 2009 Jan-Mar;8(1):26-33
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  • [Title] Phase I-II trial of perioperative high-dose-rate brachytherapy in oral cavity and oropharyngeal cancer.
  • BACKGROUND: To determine the feasibility of combined perioperative high-dose-rate brachytherapy (PHDRB) and intermediate-dose external beam radiation therapy (EBRT) as an alternative to full-dose adjuvant EBRT in patients with unirradiated squamous cell cancer (SCC) of the oral cavity and oropharynx.
  • Patients with Stage III, IVa tumors, and some recurrent cases received concomitant cisplatin-paclitaxel chemotherapy during EBRT.
  • Eleven patients (27.5%) developed RTOG Grade 3 or greater toxicity.
  • Four patients (10%) presented complications requiring a major surgical procedure (RTOG 4), and one patient died of bleeding (RTOG 5).
  • Three complications (7.5%) occurred in the perioperative period, and 8 (20.0%) occurred more than 3 months after the completion of the treatment program.
  • CONCLUSIONS: PHDRB can be integrated into the management of patients with resected cancer of the oral cavity who are candidates to receive postoperative radiation or chemoradiation.
  • [MeSH-major] Brachytherapy / adverse effects. Carcinoma, Squamous Cell / radiotherapy. Mouth Neoplasms / radiotherapy. Oropharyngeal Neoplasms / radiotherapy

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  • (PMID = 19041280.001).
  • [ISSN] 1538-4721
  • [Journal-full-title] Brachytherapy
  • [ISO-abbreviation] Brachytherapy
  • [Language] eng
  • [Publication-type] Clinical Trial, Phase I; Clinical Trial, Phase II; Journal Article
  • [Publication-country] United States
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17. Arnold DJ, Goodwin WJ, Weed DT, Civantos FJ: Treatment of recurrent and advanced stage squamous cell carcinoma of the head and neck. Semin Radiat Oncol; 2004 Apr;14(2):190-5
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Treatment of recurrent and advanced stage squamous cell carcinoma of the head and neck.
  • Despite advances in our ability to safely treat patients with recurrent cancer of the upper aerodigestive tract, outcomes for retreatment are generally poor and the first chance to cure these patients remains the best chance.
  • Thorough knowledge of the outlook and options for patients with recurrent disease is also of significance in choosing therapy for patients with newly diagnosed disease.
  • This is especially true for newly diagnosed patients making the choice between surgery and nonsurgical ("organ-sparing") options, who need to know the outlook for salvage surgery, should they recur after radiation with or without concomitant chemotherapy.
  • Salvage surgery is generally the best option for previously irradiated patients who are faced with resectable, recurrent disease.
  • Unfortunately, the results of surgical salvage are generally poor for patients with advanced stage recurrence and for those who recur after treatment of advanced disease.
  • The site of initial and recurrent disease is important.
  • Surgical salvage is most effective for patients with recurrent laryngeal cancer, least effective for recurrent cancer of the pharynx, and is intermediate for recurrence in the oral cavity.
  • Patients choosing nonsurgical treatment for newly diagnosed cancer of the pharynx cannot rely on salvage surgery in the event of recurrence.
  • Reirraditation for patients who have failed initial treatment that included radiation therapy has been used at a number of institutions with some success.
  • Experience using reirradiation with or without concomitant chemotherapy continues to evolve.
  • Palliative chemotherapy is an option for most patients, but response rates are generally poor and of short duration, after failure of initial treatment that includes radiation therapy.
  • The best approach for many patients and families who face advanced recurrent disease is honest but compassionate communication and supportive care with the help of a hospice organization.
  • [MeSH-major] Carcinoma, Squamous Cell / therapy. Head and Neck Neoplasms / therapy. Neoplasm Recurrence, Local / therapy
  • [MeSH-minor] Humans. Retreatment / methods. Salvage Therapy / methods

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  • (PMID = 15095264.001).
  • [ISSN] 1053-4296
  • [Journal-full-title] Seminars in radiation oncology
  • [ISO-abbreviation] Semin Radiat Oncol
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Number-of-references] 15
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18. Langer CJ, Harris J, Horwitz EM, Nicolaou N, Kies M, Curran W, Wong S, Ang K: Phase II study of low-dose paclitaxel and cisplatin in combination with split-course concomitant twice-daily reirradiation in recurrent squamous cell carcinoma of the head and neck: results of Radiation Therapy Oncology Group Protocol 9911. J Clin Oncol; 2007 Oct 20;25(30):4800-5
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  • [Title] Phase II study of low-dose paclitaxel and cisplatin in combination with split-course concomitant twice-daily reirradiation in recurrent squamous cell carcinoma of the head and neck: results of Radiation Therapy Oncology Group Protocol 9911.
  • PURPOSE: Recurrent squamous cell carcinoma of the head and neck (SCCHN) or new second primary tumor (SPT) in a previous radiation field, if not curable by surgery or radiation, is almost always fatal.
  • Chemotherapy alone yields a median survival time (MST) of no more than 10 months and 1-year overall survival (OS) of 35% at best.
  • Concurrent reirradiation and chemotherapy is an alternative strategy.
  • PATIENTS AND METHODS: Eligibility for Radiation Therapy Oncology Group (RTOG) protocol 9911 stipulated recurrent SCCHN or SPT in a previous radiation field.
  • Patients received twice-daily radiation (1.5 Gy per fraction bid x 5 days every 2 weeks x4), plus cisplatin 15 mg/m2 intravenously (IV) daily x 5 and paclitaxel 20 mg/m2 IV daily x 5 every 2 weeks x4.
  • Oropharynx (40%) and oral cavity (27%) were the predominant primary sites.
  • Median prior radiation dose was 65.4 Gy.
  • Seventy-four percent of patients completed chemotherapy.
  • Eight treatment-related deaths (8%) occurred: five in the acute setting, three late (including two carotid hemorrhages).
  • CONCLUSION: Despite a high incidence of grade 5 toxicity, 1- and 2-year OS rates for split-course bid radiation therapy and concurrent cisplatin/paclitaxel exceed results generally seen with chemotherapy alone.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Carcinoma, Squamous Cell / therapy. Head and Neck Neoplasms / drug therapy. Head and Neck Neoplasms / radiotherapy. Neoplasm Recurrence, Local / drug therapy. Neoplasm Recurrence, Local / radiotherapy
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Cisplatin / administration & dosage. Combined Modality Therapy. Dose Fractionation. Female. Humans. Male. Maximum Tolerated Dose. Middle Aged. Paclitaxel / administration & dosage. Survival Rate


19. Kubota A, Furukawa M, Kawano T, Komatsu M: [Nedaplatin for recurrent cancer of the head and neck]. Nihon Jibiinkoka Gakkai Kaiho; 2004 May;107(5):475-82
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  • [Title] [Nedaplatin for recurrent cancer of the head and neck].
  • This study was undertaken to evaluate the clinical efficacy and toxicity of Nedaplatin (254-S) alone or combined for UFT for recurrent head and neck cancers in an outpatient setting.
  • Thirty-two patients, previously treated, (30 men and 2 women, mean age 59 years, twenty one with loco-regional recurrence and 11 with distant metastasis, 29 with squamous cell carcinoma, 2 with adenocarcinoma and one with adenoid cystic carcinoma) were treated with Nedaplatin (254-S) alone or combined with UFT.
  • The primary site was identified in the oropharynx in 8 patients, oral cavity in 7, larynx in 5, nasopharynx in 4, hypopharynx in 3, sinuses in one, parotid in one, and unknown primary in one patient.
  • The 254-S administration was repeated at 4 week intervals, and in some patients was combined with daily oral administration of 400 mg of UFT-E (tegafur-uracil enterogranules).
  • Treatment with 254-S alone or combined UFT-E could be conducted in an outpatient setting and was able to improve the overall survival rate for recurrent head and neck cancer.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Head and Neck Neoplasms / drug therapy. Organoplatinum Compounds / therapeutic use
  • [MeSH-minor] Adenocarcinoma / drug therapy. Adult. Aged. Antineoplastic Combined Chemotherapy Protocols / administration & dosage. Carcinoma, Adenoid Cystic / drug therapy. Carcinoma, Squamous Cell / drug therapy. Female. Humans. Male. Middle Aged. Survival Rate. Tegafur / administration & dosage. Uracil / administration & dosage

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  • (PMID = 15198007.001).
  • [ISSN] 0030-6622
  • [Journal-full-title] Nihon Jibiinkoka Gakkai kaiho
  • [ISO-abbreviation] Nippon Jibiinkoka Gakkai Kaiho
  • [Language] jpn
  • [Publication-type] English Abstract; Journal Article
  • [Publication-country] Japan
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Organoplatinum Compounds; 1548R74NSZ / Tegafur; 56HH86ZVCT / Uracil; 8UQ3W6JXAN / nedaplatin; 1-UFT protocol
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20. Andreadis C, Vahtsevanos K, Sidiras T, Thomaidis I, Antoniadis K, Mouratidou D: 5-Fluorouracil and cisplatin in the treatment of advanced oral cancer. Oral Oncol; 2003 Jun;39(4):380-5
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  • [Title] 5-Fluorouracil and cisplatin in the treatment of advanced oral cancer.
  • The benefit of the effect of chemotherapy in patients with advanced head and neck squamous cell tumors have been demonstrated by recent meta-analyses of randomized studies.
  • However, the role of chemotherapy-especially in advanced oral cancer-is not fully clear, because of the very small amount of phase II literature available.
  • From January 1994 to December 2000, a total of 44 pts aged 33-75 years (mean age 60 years) with advanced and histologically proved squamous cell carcinoma's of the oral cavity received at least one chemotherapy course.
  • The chemotherapy was the initial therapy in a group of 21 patients.
  • In a second group of 23 patients the chemotherapy was delivered after relapse of their disease.
  • The pre-chemotherapy treatment of the second group was radiotherapy in 11, surgery in 4, combination of radiotherapy and surgery in 8 patients.
  • The chemotherapy regimen consisted of cisplatin 100 mg/m(2) in 3-h infusion, day 1 and 5-FU 1000 mg/m(2) in 24-h infusion, days 1-5.
  • Treatment was repeated every 21 days.
  • A total of 154 treatment courses (3.5 per patient, ranged 1-10) were administered.
  • Myelotoxicity, nausea and vomiting were the major treatment complications.
  • The overall response rate to the induction chemotherapy was 52.3%, with 19% complete (CR), and 33.3% partial response's (PR) and to the chemotherapy for recurrent/metastatic disease 30.4% with 8.7% CR, and 21.7% PR.
  • Chemotherapy with cisplatin and 5-FU combination is effective in pts with advanced squamous cell oral cancer and appears to improve the survival of patients who have a good response.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Carcinoma, Squamous Cell / drug therapy. Mouth Neoplasms / drug therapy. Neoplasm Recurrence, Local / drug therapy
  • [MeSH-minor] Adult. Aged. Chi-Square Distribution. Cisplatin / administration & dosage. Cisplatin / adverse effects. Female. Fluorouracil / administration & dosage. Fluorouracil / adverse effects. Follow-Up Studies. Humans. Male. Middle Aged. Neoplasm Staging. Patient Selection. Retrospective Studies. Salvage Therapy. Survival Rate

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  • [Copyright] Copyright 2003 Elsevier Science Ltd.
  • (PMID = 12676258.001).
  • [ISSN] 1368-8375
  • [Journal-full-title] Oral oncology
  • [ISO-abbreviation] Oral Oncol.
  • [Language] eng
  • [Publication-type] Clinical Trial; Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] Q20Q21Q62J / Cisplatin; U3P01618RT / Fluorouracil
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21. Kasperts N, Slotman B, Leemans CR, Langendijk JA: A review on re-irradiation for recurrent and second primary head and neck cancer. Oral Oncol; 2005 Mar;41(3):225-43
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  • [Title] A review on re-irradiation for recurrent and second primary head and neck cancer.
  • The purpose of this paper is to review the results of studies regarding radiation as primary or adjuvant treatment modality for head and neck recurrences or second primary tumours (SPT) in previously irradiated areas, with emphasis on acute and late radiation induced morbidity, locoregional control and survival.
  • (1) re-irradiation for locoregional recurrent disease or SPT in the head and neck region, (2) squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx and larynx, and (3) a minimum of 10 patients included in the study.
  • Studies were divided in four categories, including (1) external beam re-irradiation, (2) re-irradiation with brachytherapy, (3) re-irradiation in combination with chemotherapy and (4) postoperative re-irradiation.
  • Most studies were retrospective using heterogeneous treatment regimens and including heterogeneous groups of patients.
  • High dose reirradiation as salvage treatment in case of recurrent or second primary head and neck cancer should be considered, particularly when salvage surgery is not feasible.
  • Although long term survivors are reported is some studies, the relatively high incidence of treatment-related morbidity emphasize the need for further optimisation in order to improve locoregional control and reduce the risk on late morbidity.
  • [MeSH-minor] Brachytherapy. Combined Modality Therapy. Humans. Morbidity. Retreatment. Survival Rate. Treatment Outcome

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  • [CommentIn] Oral Oncol. 2005 Oct;41(9):953-4 [15935725.001]
  • (PMID = 15743686.001).
  • [ISSN] 1368-8375
  • [Journal-full-title] Oral oncology
  • [ISO-abbreviation] Oral Oncol.
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] England
  • [Number-of-references] 61
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22. Sher DJ, Haddad RI, Norris CM Jr, Posner MR, Wirth LJ, Goguen LA, Annino D, Balboni T, Allen A, Tishler RB: Efficacy and toxicity of reirradiation using intensity-modulated radiotherapy for recurrent or second primary head and neck cancer. Cancer; 2010 Oct 15;116(20):4761-8
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  • [Title] Efficacy and toxicity of reirradiation using intensity-modulated radiotherapy for recurrent or second primary head and neck cancer.
  • BACKGROUND: Patients with locally recurrent squamous cell cancer of the head and neck (SCCHN) are reported to have a poor prognosis and limited therapeutic options.
  • This study reported the experience of the Dana-Farber Cancer Institute (DFCI) with IMRT-based chemoradiotherapy with or without surgery for locally recurrent SCCHN.
  • METHODS: The current study was a retrospective study of all patients treated at DFCI who were diagnosed with nonmetastatic second primary or recurrent SCCHN and who received reirradiation based on IMRT.
  • Recurrent disease was treated in the oral cavity (4 patients), larynx/hypopharynx (13 patients), oropharynx (7 patients), nasopharynx (2 patients), and neck (9 patients).
  • The median radiation dose was 60 Gray (Gy), and all patients received concurrent chemotherapy.
  • Approximately 91% and 46%, respectively, of all patients developed at least 1 acute and late grade 3 toxicity.
  • [MeSH-major] Carcinoma, Squamous Cell / radiotherapy. Head and Neck Neoplasms / radiotherapy. Neoplasms, Second Primary / radiotherapy. Radiotherapy, Intensity-Modulated
  • [MeSH-minor] Combined Modality Therapy. Female. Humans. Male. Middle Aged. Neoplasm Recurrence, Local / radiotherapy. Retreatment. Retrospective Studies. Survival Analysis

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  • [Copyright] © 2010 American Cancer Society.
  • (PMID = 20572036.001).
  • [ISSN] 0008-543X
  • [Journal-full-title] Cancer
  • [ISO-abbreviation] Cancer
  • [Language] eng
  • [Publication-type] Evaluation Studies; Journal Article
  • [Publication-country] United States
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23. Day TA, Davis BK, Gillespie MB, Joe JK, Kibbey M, Martin-Harris B, Neville B, Richardson MS, Rosenzweig S, Sharma AK, Smith MM, Stewart S, Stuart RK: Oral cancer treatment. Curr Treat Options Oncol; 2003 Feb;4(1):27-41
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  • [Title] Oral cancer treatment.
  • Oral cancer is the sixth most common cancer in the world, and it continues to represent a serious public health problem.
  • Oral cancer is a preventable disease, related to behavioral and lifestyle factors, including tobacco and alcohol.
  • Prevention and early detection of oral cancer remain the goals of national efforts to reduce the impact of this disease on the public.
  • Surgical treatment is the mainstay of therapy for patients with oral cancer, particularly in advanced stages of cancer.
  • External beam radiation therapy and brachytherapy have been used successfully as the primary modality for treating patients with early stage oral cancer, and they are the standard of care for use as adjuvant therapy in postoperative cases of patients with advanced stage oral cancer.
  • There is an emerging trend for the use of chemotherapy in combination with radiation therapy and surgery for patients with advanced, recurrent, and metastatic head and neck cancer, although evidence is limited regarding survival benefit when used for treating patients with oral cavity carcinoma.
  • Any report on the treatment of oral cancer is incomplete without consideration of functional and aesthetic outcomes, particularly addressing speech, swallowing, masticatory efficiency, and dental rehabilitation.
  • Future generations will continue to fight these dreadful diseases until scientists and clinicians are provided the opportunities to expand efforts to prevent, detect (early), and eradicate oral and other head and neck cancers.
  • [MeSH-major] Mouth Neoplasms / surgery
  • [MeSH-minor] Clinical Trials as Topic. Combined Modality Therapy. Diet. Humans. Life Style. Microsurgery. Oral Surgical Procedures

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  • (PMID = 12525277.001).
  • [ISSN] 1527-2729
  • [Journal-full-title] Current treatment options in oncology
  • [ISO-abbreviation] Curr Treat Options Oncol
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Number-of-references] 113
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24. Porceddu SV, Campbell B, Rischin D, Corry J, Weih L, Guerrieri M, Grossi M, Peters LJ: Postoperative chemoradiotherapy for high-risk head-and-neck squamous cell carcinoma. Int J Radiat Oncol Biol Phys; 2004 Oct 1;60(2):365-73
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  • [Title] Postoperative chemoradiotherapy for high-risk head-and-neck squamous cell carcinoma.
  • PURPOSE: To describe the use of postoperative concurrent chemoradiotherapy, with either weekly cisplatin or carboplatin, for high-risk head-and-neck squamous cell carcinoma (HNSCC) in a single institutional setting.
  • The predominant primary site was the oral cavity in 24 patients (51%), 27 had nodal disease with extracapsular extension, and 26 had positive or close mucosal margins (<5 mm).
  • Ten patients had undergone resection of recurrent disease after previous surgery.
  • The median radiotherapy dose was 60 Gy (range, 50-66 Gy).
  • Of the 47 patients, 45 (96%) completed at least four of the six planned doses of chemotherapy and 45 (96%) completed the planned course of radiotherapy.
  • No treatment-related deaths occurred.
  • Five cases of Grade 3-4 late treatment-related sequelae developed.
  • CONCLUSION: Treatment with postoperative concurrent weekly cisplatin or carboplatin and radiotherapy was reasonably well tolerated.
  • Patients treated after resection of recurrent disease (after previous surgery alone) fared worse than those treated at the initial resection.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Carboplatin / therapeutic use. Carcinoma, Squamous Cell / drug therapy. Carcinoma, Squamous Cell / radiotherapy. Cisplatin / therapeutic use. Head and Neck Neoplasms / drug therapy. Head and Neck Neoplasms / radiotherapy
  • [MeSH-minor] Adult. Aged. Combined Modality Therapy. Confidence Intervals. Disease-Free Survival. Female. Humans. Male. Middle Aged. Neck Dissection. Radiation Injuries / etiology. Radiotherapy Dosage. Regression Analysis. Survival Rate


25. Wutzl A, Ploder O, Kermer C, Millesi W, Ewers R, Klug C: Mortality and causes of death after multimodality treatment for advanced oral and oropharyngeal cancer. J Oral Maxillofac Surg; 2007 Feb;65(2):255-60
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  • [Title] Mortality and causes of death after multimodality treatment for advanced oral and oropharyngeal cancer.
  • PURPOSE: To analyze mortality and causes of death in patients who received preoperative radiochemotherapy and underwent radical surgery for advanced oral or oropharyngeal cancer.
  • PATIENTS AND METHODS: A total of 222 patients who underwent multimodality treatment from 1990 to 2000 were included in the study.
  • The inclusion criterion was International Union Against Cancer (UICC) disease stage II to IV (T2, 33.3%; T3, 12.6%; T4, 54.1%).
  • Patients received preoperative radiotherapy 50 Gy and concomitant chemotherapy with mitomycin and 5-fluorouracil.
  • Of these, a second cancer in the head and neck region or the lower respiratory tract or the upper digestive tract was found in 7.3%.
  • Although 93% of deaths related to recurrent disease occurred within the first 36 months after surgery, the remaining causes of death did not reveal a specific temporal pattern.
  • CONCLUSION: Favorable survival data were registered for patients with advanced squamous cell carcinoma of the oral cavity who underwent combined treatment protocols.
  • Because recurrent disease is a less common cause of mortality than are other causes, the latter should receive attention during surveillance.
  • [MeSH-major] Carcinoma, Squamous Cell / mortality. Carcinoma, Squamous Cell / therapy. Mouth Neoplasms / mortality. Mouth Neoplasms / therapy
  • [MeSH-minor] Cause of Death. Chemotherapy, Adjuvant. Disease-Free Survival. Female. Humans. Male. Middle Aged. Neoplasm Recurrence, Local / mortality. Neoplasms, Second Primary / mortality. Oropharyngeal Neoplasms / mortality. Oropharyngeal Neoplasms / surgery. Oropharyngeal Neoplasms / therapy. Radiotherapy, Adjuvant. Retrospective Studies. Time Factors

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  • (PMID = 17236930.001).
  • [ISSN] 0278-2391
  • [Journal-full-title] Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons
  • [ISO-abbreviation] J. Oral Maxillofac. Surg.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
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26. Lorenz KJ, Maier H: [Squamous cell carcinoma of the head and neck. Photodynamic therapy with Foscan]. HNO; 2008 Apr;56(4):402-9
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  • [Title] [Squamous cell carcinoma of the head and neck. Photodynamic therapy with Foscan].
  • [Transliterated title] Plattenepithelkarzinome im Kopf-Hals-Bereich. Photodynamische Therapie mit Foscan.
  • INTRODUCTION: Photodynamic therapy (PDT) is a relatively new method of treating superficial tumours of the skin or mucous membranes.
  • PATIENTS AND METHODS: From November 2004 to February 2006, a total of 24 patients with recurrent or secondary tumours after squamous cell carcinoma of the head and neck were treated with PDT at the German Armed Forces Hospital in Ulm after other treatment options had failed.
  • Three patients did not respond to treatment.
  • The mean duration of overall survival was 305.7 days (+/-199.4) after completion of treatment.
  • CONCLUSIONS: Photodynamic therapy is an important treatment option for patients who develop recurrent or secondary tumours after squamous cell carcinoma of the upper aerodigestive tract and fail to respond to other treatments.
  • In addition, PDT may play a role in the primary treatment of superficial tumours of the oral cavity, pharynx and larynx in the future.
  • [MeSH-major] Carcinoma, Squamous Cell / drug therapy. Head and Neck Neoplasms / drug therapy. Mesoporphyrins / therapeutic use. Photochemotherapy / methods
  • [MeSH-minor] Aged. Aged, 80 and over. Antineoplastic Agents / therapeutic use. Disease-Free Survival. Female. Humans. Male. Middle Aged. Photosensitizing Agents / therapeutic use. Treatment Outcome

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  • [Cites] Radiother Oncol. 1995 Aug;36(2):94-100 [7501817.001]
  • [Cites] Laryngoscope. 1994 Apr;104(4):399-403 [8164476.001]
  • [Cites] Eur Arch Otorhinolaryngol. 2000;257(3):164-7 [10839492.001]
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  • (PMID = 17516041.001).
  • [ISSN] 1433-0458
  • [Journal-full-title] HNO
  • [ISO-abbreviation] HNO
  • [Language] ger
  • [Publication-type] Clinical Trial; English Abstract; Journal Article
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Mesoporphyrins; 0 / Photosensitizing Agents; FU21S769PF / temoporfin
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27. Kübler AC, de Carpentier J, Hopper C, Leonard AG, Putnam G: Treatment of squamous cell carcinoma of the lip using Foscan-mediated photodynamic therapy. Int J Oral Maxillofac Surg; 2001 Dec;30(6):504-9
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  • [Title] Treatment of squamous cell carcinoma of the lip using Foscan-mediated photodynamic therapy.
  • Carcinoma of the lip is a common cancer of the head and neck area; its incidence is approximately one-quarter that for oral cavity cancers.
  • This non-randomized Phase II study aimed to estimate the complete response (CR) rate to Foscan-mediated photodynamic therapy (Foscan-PDT) in patients with primary cancer of the lip, duration of CR, and the tolerability and safety of Foscan-PDT.
  • Twenty-five patients with squamous cell carcinoma (SCC) of the lip (Tis, T1, T2/N0/M0) and Karnofsky status > or = 70 received 0.15 mg/kg Foscan intravenously, followed 4 days later by a single non-thermal illumination of the tumour (light dose 20 J/cm2, irradiance 100 mW/cm2, lambda=652 nm).
  • The most common adverse event was swelling and local pain at the treatment site.
  • One patient developed a single lymph node metastasis 7 months after therapy.
  • The functional results were excellent in all patients without any signs of limited mouth opening or impaired lip closure.
  • The cosmetic outcome was better than after surgical therapy.
  • Foscan-PDT is an effective treatment modality for small primary tumours of the lips.
  • It allows preservation of form and function and does not compromise future treatment options for recurrent, residual or second primary disease.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Carcinoma, Squamous Cell / drug therapy. Lip Neoplasms / drug therapy. Mesoporphyrins / therapeutic use. Photosensitizing Agents / therapeutic use
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Biopsy. Female. Follow-Up Studies. Humans. Injections, Intravenous. Laser Therapy. Lymphatic Metastasis. Male. Middle Aged. Neoplasm Recurrence, Local / pathology. Neoplasm Staging. Photosensitivity Disorders / chemically induced. Prospective Studies. Radiation Dosage. Remission Induction. Safety. Treatment Outcome

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  • (PMID = 11829232.001).
  • [ISSN] 0901-5027
  • [Journal-full-title] International journal of oral and maxillofacial surgery
  • [ISO-abbreviation] Int J Oral Maxillofac Surg
  • [Language] eng
  • [Publication-type] Clinical Trial; Clinical Trial, Phase II; Comparative Study; Journal Article; Multicenter Study
  • [Publication-country] Denmark
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Mesoporphyrins; 0 / Photosensitizing Agents; FU21S769PF / temoporfin
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28. Karakoyun-Celik O, Norris CM Jr, Tishler R, Mahadevan A, Clark JR, Goldberg S, Devlin P, Busse PM: Definitive radiotherapy with interstitial implant boost for squamous cell carcinoma of the tongue base. Head Neck; 2005 May;27(5):353-61
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  • [Title] Definitive radiotherapy with interstitial implant boost for squamous cell carcinoma of the tongue base.
  • BACKGROUND: The purpose of this study was to examine the long-term outcome of a cohort of patients with unresected base of tongue carcinoma who received interstitial brachytherapy after comprehensive external beam radiation therapy.
  • METHODS: Between 1983 and 2000, 122 patients with primary or recurrent squamous cell carcinoma of the oropharynx or oral cavity received interstitial brachytherapy as part of their overall management.
  • Forty patients had primary, unresected carcinoma of the base of tongue and are the subjects of this analysis.
  • Twenty-four (60%) received two to three cycles of neoadjuvant chemotherapy.
  • The oropharynx, bilateral neck, and supraclavicular fossae were comprehensively irradiated, and the tongue base received a median external beam dose of 61.2 Gy (50-72 Gy).
  • The primary site was then boosted with an interstitial 192Iridium implant by use of a gold-button single-strand technique and three-dimensional treatment planning.
  • The dose rate was prescribed at 0.4 to 0.5 Gy/hr.
  • The median implant dose was 17.4 Gy (9.6-24 Gy) and adjusted to reach a total dose to the primary tumor of 80 Gy.
  • N2 to 3 disease was managed by a planned neck dissection performed at the time of the implant.
  • Systemic therapy was associated with an improvement in overall survival (p = .04) and a trend toward increased primary site control with greater clinical response.
  • CONCLUSIONS: In an era of greatly improved dose distributions made possible by three-dimensional treatment planning and intensity-modulated radiation therapy, brachytherapy allows a highly conformal dose to be delivered in sites such as the oropharynx.
  • If done properly, the procedure is safe and delivers a dose that is higher than what can be achieved by external beam radiation alone with the expected biologic advantages.
  • [MeSH-major] Brachytherapy / methods. Carcinoma, Squamous Cell / therapy. Tongue Neoplasms / therapy
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Chemotherapy, Adjuvant. Dose-Response Relationship, Radiation. Female. Follow-Up Studies. Humans. Iridium Radioisotopes / therapeutic use. Male. Middle Aged. Radiotherapy Dosage. Radiotherapy, Computer-Assisted. Treatment Outcome

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  • [Copyright] 2005 Wiley Periodicals, Inc.
  • (PMID = 15726587.001).
  • [ISSN] 1043-3074
  • [Journal-full-title] Head & neck
  • [ISO-abbreviation] Head Neck
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Iridium Radioisotopes
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29. Lorenz KJ, Maier H: Photodynamic therapy with meta-tetrahydroxyphenylchlorin (Foscan) in the management of squamous cell carcinoma of the head and neck: experience with 35 patients. Eur Arch Otorhinolaryngol; 2009 Dec;266(12):1937-44
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  • [Title] Photodynamic therapy with meta-tetrahydroxyphenylchlorin (Foscan) in the management of squamous cell carcinoma of the head and neck: experience with 35 patients.
  • Photodynamic therapy (PDT) is a relatively new method of treating superficial tumours of the skin and mucosa.
  • From November 2003 to July 2007, a total of 35 patients with recurrent squamous cell carcinoma or secondary tumours of the head and neck region were treated with PDT at the German Armed Forces Hospital in Ulm.
  • These patients had failed or found unsuitable for other treatments.
  • Four patients (11.5%) did not respond to PDT treatment.
  • The mean duration of overall survival was 401.45 (+/-321.2) days, median was 356 after the completion of treatment.
  • None of the patient developed serious complications.
  • Photodynamic therapy is an important treatment option for patients who present with recurrent carcinoma or secondary tumours of the upper aerodigestive tract and who have failed or unsuitable for other treatments.
  • Due to the excellent treatment results that have been achieved so far, PDT may in the future also play a role in the primary treatment of superficial tumours of the oral cavity, pharynx and larynx.
  • [MeSH-major] Carcinoma, Squamous Cell / drug therapy. Head and Neck Neoplasms / drug therapy. Mesoporphyrins / therapeutic use. Photochemotherapy / methods. Photosensitizing Agents / therapeutic use
  • [MeSH-minor] Aged. Aged, 80 and over. Disease-Free Survival. Female. Follow-Up Studies. Germany / epidemiology. Humans. Injections, Intravenous. Magnetic Resonance Imaging. Male. Middle Aged. Positron-Emission Tomography. Retrospective Studies. Survival Rate. Tomography, X-Ray Computed. Treatment Outcome

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  • (PMID = 19290535.001).
  • [ISSN] 1434-4726
  • [Journal-full-title] European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery
  • [ISO-abbreviation] Eur Arch Otorhinolaryngol
  • [Language] eng
  • [Publication-type] Comparative Study; Journal Article
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / Mesoporphyrins; 0 / Photosensitizing Agents; FU21S769PF / temoporfin
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30. van Veen RL, Nyst H, Rai Indrasari S, Adham Yudharto M, Robinson DJ, Tan IB, Meewis C, Peters R, Spaniol S, Stewart FA, Levendag PC, Sterenborg HJ: In vivo fluence rate measurements during Foscan-mediated photodynamic therapy of persistent and recurrent nasopharyngeal carcinomas using a dedicated light applicator. J Biomed Opt; 2006 Jul-Aug;11(4):041107

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  • [Title] In vivo fluence rate measurements during Foscan-mediated photodynamic therapy of persistent and recurrent nasopharyngeal carcinomas using a dedicated light applicator.
  • The objective of this study was to evaluate the performance of a dedicated light applicator for light delivery and fluence rate monitoring during Foscan-mediated photodynamic therapy of nasopharyngeal carcinoma in a clinical phase I/II study.
  • We have developed a flexible silicone applicator that can be inserted through the mouth and fixed in the nasopharyngeal cavity.
  • Three isotropic fibers, for measuring of the fluence (rate) during therapy, were located within the nasopharyngeal tumor target area and one was manually positioned to monitor structures at risk in the shielded area.
  • A flexible black silicon patch tailored to the patient's anatomy is attached to the applicator to shield the soft palate and oral cavity from the 652-nm laser light.
  • We observed a systematic reduction in fluence rate during therapy in 20 out of 26 illuminations, which may be related to photodynamic therapy-induced increased blood content, decreased oxygenation, or reduced scattering.
  • The average light distribution in the target area was reasonably uniform over the length of the applicator, thus giving an acceptably homogeneous illumination throughout the cavity.
  • [MeSH-major] Lighting / instrumentation. Mesoporphyrins / therapeutic use. Nasopharyngeal Neoplasms / drug therapy. Neoplasm Recurrence, Local / drug therapy. Photochemotherapy / instrumentation
  • [MeSH-minor] Adolescent. Adult. Equipment Design. Equipment Failure Analysis. Female. Humans. Indonesia. Light. Male. Photosensitizing Agents / therapeutic use. Pilot Projects. Radiation Dosage. Radiometry. Treatment Outcome

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  • (PMID = 16965135.001).
  • [ISSN] 1083-3668
  • [Journal-full-title] Journal of biomedical optics
  • [ISO-abbreviation] J Biomed Opt
  • [Language] eng
  • [Publication-type] Clinical Trial, Phase I; Clinical Trial, Phase II; Journal Article; Multicenter Study
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Mesoporphyrins; 0 / Photosensitizing Agents; FU21S769PF / temoporfin
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31. Agra IM, Carvalho AL, Pontes E, Campos OD, Ulbrich FS, Magrin J, Kowalski LP: Postoperative complications after en bloc salvage surgery for head and neck cancer. Arch Otolaryngol Head Neck Surg; 2003 Dec;129(12):1317-21
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  • [Title] Postoperative complications after en bloc salvage surgery for head and neck cancer.
  • OBJECTIVE: To analyze the frequency of and risk factors for postoperative complications after en bloc salvage surgery for head and neck cancer.
  • SETTING: Patients were evaluated from February 7, 1990, to November 17, 1999, in a tertiary cancer center hospital.
  • Only patients with recurrent head and neck squamous cell carcinoma undergoing en bloc salvage resection were eligible for the study.
  • RESULTS: The tumor location was the lip in 6 patients, oral cavity in 55, oropharynx in 31, larynx in 24, and hypopharynx in 8.
  • Previous treatment was surgery alone in 20 patients, radiotherapy alone in 68, surgery and radiotherapy in 21, and radiotherapy and chemotherapy in 14.
  • An additional patient received chemotherapy alone before salvage surgery.
  • The clinical stage of the recurrent tumor was I or II in 23 patients and III or IV in 101 patients.
  • The major factor associated with the overall occurrence of postoperative complications was the clinical stage of the recurrent tumor (P =.02).
  • The occurrence of minor complications correlated with the previously treated site, with complications occurring more often in patients undergoing locoregional vs local treatment (P =.04).
  • Major complications were associated with the time between initial treatment and salvage surgery (P =.05).
  • The clinical stage of the recurrent tumor and the previous site treated were the 2 major factors associated with the occurrence of postoperative complications.
  • [MeSH-major] Carcinoma, Squamous Cell / surgery. Head and Neck Neoplasms / surgery. Neoplasm Recurrence, Local / surgery. Postoperative Complications / etiology. Salvage Therapy / adverse effects
  • [MeSH-minor] Adolescent. Adult. Aged. Aged, 80 and over. Combined Modality Therapy. Female. Humans. Length of Stay / statistics & numerical data. Logistic Models. Male. Middle Aged. Morbidity. Multivariate Analysis. Neoplasm Staging. Prognosis. Retrospective Studies. Risk Factors. Survival Analysis. Time Factors. Treatment Outcome

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  • (PMID = 14676158.001).
  • [ISSN] 0886-4470
  • [Journal-full-title] Archives of otolaryngology--head & neck surgery
  • [ISO-abbreviation] Arch. Otolaryngol. Head Neck Surg.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
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32. Rigual NR, Thankappan K, Cooper M, Sullivan MA, Dougherty T, Popat SR, Loree TR, Biel MA, Henderson B: Photodynamic therapy for head and neck dysplasia and cancer. Arch Otolaryngol Head Neck Surg; 2009 Aug;135(8):784-8
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  • [Title] Photodynamic therapy for head and neck dysplasia and cancer.
  • OBJECTIVE: To determine the response of dysplasia, carcinoma in situ (CIS), and T1 carcinoma of the oral cavity and larynx to photodynamic therapy with porfimer sodium.
  • SETTING: A National Cancer Institute-designated cancer institute.
  • PATIENTS: Patients with primary or recurrent moderate to severe oral or laryngeal dysplasia, CIS, or T1N0 carcinoma.
  • INTERVENTION: Porfimer sodium, 2 mg/kg of body weight, was injected intravenously 48 hours before treatment.
  • The light dose was 50 J/cm(2) for dysplasia and CIS and 75 J/cm(2) for carcinoma.
  • Posttreatment biopsies were performed in all patients with persistent and recurrent visible lesions.
  • Three patients with oral dysplasia with an initial CR experienced recurrence in the treatment field.
  • All the patients with NR, a PR, or recurrence after an initial CR underwent salvage treatment.
  • CONCLUSION: Photodynamic therapy with porfimer sodium is an effective treatment alternative, with no permanent sequelae, for oral and laryngeal dysplasia and early carcinoma.
  • [MeSH-major] Carcinoma in Situ / drug therapy. Dihematoporphyrin Ether / administration & dosage. Head and Neck Neoplasms / drug therapy. Low-Level Light Therapy / methods. Photochemotherapy / methods. Photosensitizing Agents / administration & dosage. Precancerous Conditions / drug therapy
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Female. Humans. Male. Middle Aged. Neoplasm Staging. Prospective Studies. Treatment Outcome

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  • (PMID = 19687399.001).
  • [ISSN] 1538-361X
  • [Journal-full-title] Archives of otolaryngology--head & neck surgery
  • [ISO-abbreviation] Arch. Otolaryngol. Head Neck Surg.
  • [Language] eng
  • [Databank-accession-numbers] ClinicalTrials.gov/ NCT00530088
  • [Grant] United States / NCI NIH HHS / CA / P01 CA055791; United States / NCI NIH HHS / CA / P01 CA055791-16
  • [Publication-type] Clinical Trial; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Photosensitizing Agents; 97067-70-4 / Dihematoporphyrin Ether
  • [Other-IDs] NLM/ NIHMS166203; NLM/ PMC2810853
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33. Cripps C, Winquist E, Devries MC, Stys-Norman D, Gilbert R, Head and Neck Cancer Disease Site Group: Epidermal growth factor receptor targeted therapy in stages III and IV head and neck cancer. Curr Oncol; 2010 Jun;17(3):37-48
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  • [Title] Epidermal growth factor receptor targeted therapy in stages III and IV head and neck cancer.
  • QUESTION: What are the benefits associated with the use of anti-epidermal growth factor receptor (anti-EGFR) therapies in squamous cell carcinoma of the head and neck (HNSCC)?
  • Anti-EGFR therapies of interest included cetuximab, gefitinib, lapatinib, zalutumumab, erlotinib, and panitumumab.
  • PERSPECTIVES: Head-and-neck cancer includes malignant tumours arising from a variety of sites in the upper aerodigestive tract.
  • The most common histologic type is squamous cell carcinoma, and most common sites are the oral cavity, the oropharynx, the hypopharynx, and the larynx.
  • Worldwide, HNSCC is the sixth most common neoplasm, and despite advances in therapy, long-term survival in HNSCC patients is poor.
  • Primary surgery followed by chemoradiation, or primary chemoradiation, are the standard treatment options for patients with locally advanced (stages III-IVB) HNSCC; however, meta-analytic data indicate that the benefit of concurrent platinum-based chemotherapy disappears in patients over the age of 70 years.
  • Cetuximab is a monoclonal antibody approved for use in combination with radiation in the treatment of patients with untreated locally advanced HNSCC and as monotherapy for patients with recurrent or metastatic (stage IVC) HNSCC who have progressed on platinum-based therapy.
  • Given the interest in anti-EGFR agents in advanced HNSCC, the Head and Neck Cancer Disease Site Group (DSG) of Cancer Care Ontario's Program in Evidence-Based Care (PEBC) chose to systematically review the literature pertaining to this topic so as to develop evidence-based recommendations for treatment.
  • OUTCOMES: Outcomes of interest included overall and progression-free survival, quality of life, tumour response rate and duration, and the toxicity associated with the use of anti-EGFR therapies.
  • The resulting recommendations were approved by the Report Approval Panel of the PEBC, and by the Head and Neck Cancer DSG.
  • The randomized controlled trials (RCTS) involved three distinct patient populations: those with locally advanced HNSCC being treated for cure, those with incurable advanced recurrent or metastatic HNSCC being treated with first-line platinum-based chemotherapy, and those with incurable advanced recurrent or metastatic HNSCC who had disease progression despite, or who were unsuitable for, first-line platinum-based chemotherapy.
  • PRACTICE GUIDELINE: These recommendations apply to adult patients with locally advanced (nonmetastatic stages iii-ivb) or recurrent or metastatic (stage IVC) HNSCC.
  • Platinum-based chemoradiation remains the current standard of care for treatment of locally advanced HNSCC.
  • In patients with locally advanced HNSCC who are medically unsuitable for concurrent platinum based chemotherapy or who are over the age of 70 years (because concurrent chemotherapy does not appear to improve overall survival in this patient population), the addition of cetuximab to radical radiotherapy should be considered to improve overall survival, progression-free survival, and time to local recurrence.Cetuximab in combination with platinum-based combination chemotherapy is superior to chemotherapy alone in patients with recurrent or metastatic HNSCC, and is recommended to improve overall survival, progression-free survival, and response rate.The role of anti-EGFR therapies in the treatment of locally advanced HNSCC is currently under study in large randomized trials, and patients with HNSCC should continue to be offered clinical trials of novel agents aimed at improving outcomes.
  • However, five ongoing trials are investigating the effect of the addition of EGFR inhibitors concurrently with, before, or after chemoradiotherapy; those trials should provide direction about the best integration of cetuximab into standard treatment.
  • In patients with recurrent or metastatic HNSCC who experience progressive disease despite, or who are unsuitable for, first-line platinum-based chemotherapy, gefitinib at doses of 250 mg or 500 mg daily, compared with weekly methotrexate, did not increase median overall survival [hazard ratio (hr): 1.22; 96% confidence interval (ci): 0.95 to 1.57; p = 0.12 (for 250 mg daily vs. weekly methotrexate); hr: 1.12; 95% ci: 0.87 to 1.43; p = 0.39 (for 500 mg daily vs. weekly methotrexate)] or objective response rate (2.7% for 250 mg and 7.6% for 500 mg daily vs. 3.9% for weekly methotrexate, p > 0.05).

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  • (PMID = 20567625.001).
  • [ISSN] 1718-7729
  • [Journal-full-title] Current oncology (Toronto, Ont.)
  • [ISO-abbreviation] Curr Oncol
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Canada
  • [Other-IDs] NLM/ PMC2880902
  • [Keywords] NOTNLM ; Head-and-neck cancer / egfr inhibitors / epidermal growth factor receptor / overall survival / progression-free survival / tumour response rate
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34. Warde P, Kroll B, O'Sullivan B, Aslanidis J, Tew-George E, Waldron J, Maxymiw W, Liu FF, Payne D, Cummings B: A phase II study of Biotene in the treatment of postradiation xerostomia in patients with head and neck cancer. Support Care Cancer; 2000 May;8(3):203-8
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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 Biotene in the treatment of postradiation xerostomia in patients with head and neck cancer.
  • One of the major side effects of radical radiation therapy for head and neck malignancies is xerostomia, or dryness of the mouth.
  • There is no clearly effective treatment for this condition, but we have observed that patients in our practice believe that their symptoms improve significantly when using two "over-the-counter" oral comfort products - Biotene (toothpaste, mouthwash and chewing gum) and Oralbalance gel.
  • All had biopsy-proven carcinoma of the nasopharynx, oropharynx, oral cavity, hypopharynx or larynx, and had received primary radiotherapy with curative intent (> or =50 Gy in 20 fractions) more than 4 months before study entry.
  • There was no clinical evidence of recurrent disease.
  • Patients with an increase of 10 mm from their baseline score on the visual analogue scale were classified as having responded to the treatment intervention, and those with an increase of > or =25 mm from their baseline score were classified as having experienced a major improvement in their symptoms.
  • After 2 months of treatment, 15 patients (54%) reported an improvement in intraoral dryness and 10 of these patients (36%) reported a major improvement.
  • Seventeen patients (61%) reported an improvement in oral discomfort, and 12 of these (43%) had a major improvement in their symptoms.
  • [MeSH-major] Anti-Infective Agents / therapeutic use. Glucose Oxidase / therapeutic use. Head and Neck Neoplasms / radiotherapy. Lactoperoxidase / therapeutic use. Muramidase / therapeutic use. Xerostomia / drug therapy. Xerostomia / etiology
  • [MeSH-minor] Administration, Oral. Adult. Aged. Aged, 80 and over. Drug Combinations. Female. Humans. Male. Middle Aged. Radiotherapy / adverse effects. Surveys and Questionnaires. Treatment Outcome

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  • (PMID = 10789961.001).
  • [ISSN] 0941-4355
  • [Journal-full-title] Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer
  • [ISO-abbreviation] Support Care Cancer
  • [Language] eng
  • [Publication-type] Clinical Trial; Clinical Trial, Phase II; Journal Article
  • [Publication-country] GERMANY
  • [Chemical-registry-number] 0 / Anti-Infective Agents; 0 / Biotene; 0 / Drug Combinations; EC 1.1.3.4 / Glucose Oxidase; EC 1.11.1.- / Lactoperoxidase; EC 3.2.1.17 / Muramidase
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35. INGN 201: Ad-p53, Ad5CMV-p53, adenoviral p53, p53 gene therapy--introgen, RPR/INGN 201. Drugs R D; 2007;8(3):176-87
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  • [Title] INGN 201: Ad-p53, Ad5CMV-p53, adenoviral p53, p53 gene therapy--introgen, RPR/INGN 201.
  • Introgen and its wholly owned European subsidiary Gendux AB are developing an adenoviral p53 gene therapy as a treatment for cancer in the US and Europe, respectively.
  • Phase III trials in patients with head and neck cancer are ongoing, and a number of clinical trials in other cancer indications have been completed.
  • INGN 201 is being reviewed by the EMEA for approval in Li-Fraumeni syndrome (LFS) under the provisions of exceptional circumstance; the therapy is available on a compassionate use basis to eligible LFS cancer patients under a protocol authorised by the US FDA.
  • Thus replacing this gene via adenovirally-mediated p53 gene therapy is hoped to result in increased apoptosis where it is administered.INGN 201 is available for licensing, although Introgen favours retaining partial or full rights to the therapy in the US.
  • Introgen entered into a license agreement with The University of Texas System and MD Anderson Cancer Center in 1994.
  • Introgen entered into a collaboration with Rhône-Poulenc Rorer Pharmaceuticals (now sanofi-aventis) to develop therapeutics based on p53 inhibition in October 1994.
  • Introgen initiated two phase III trials in head and neck cancer (in June 2000 and May 2001) at about 80 sites in the US, Canada and Europe; the first is a comparative study of INGN 201 and IV methotrexate in 240 patients with refractory head and neck cancer.
  • The second is for the combination of INGN 201 and standard chemotherapy, compared with standard chemotherapy alone, in 288 patients with recurrent squamous cell carcinoma of the head and neck.
  • Introgen expects to complete regulatory filings for advanced recurrent head and neck cancer in the US and EU within 2007.
  • Favourable phase II data of INGN 201 in a subpopulation of patients with recurrent, unresectable head and neck cancer (SCCHN) prompted Introgen to seek accelerated approval for INGN 201 in December 2004.
  • Introgen had presented combined results from three multicentre (US and Europe) phase II studies of INGN 201 in 217 patients with recurrent squamous cell carcinoma of the head and neck confirming previous safety and efficacy results of the treatment.
  • In April 2004, the Southwest Oncology Group initiated a similar clinical trial using INGN 201 for the treatment of stage III or IV squamous cell carcinoma of the oral cavity, or oropharynx, that is able to be removed surgically.
  • The study assessed the feasibility, efficacy and safety of administering INGN 201 at the time of surgery for suppression of remaining tumour cells, followed by a combination of chemotherapy and radiation therapy.
  • The previous trial was a phase II study that afforded Introgen access to surgical specialists in cancer and complemented the company's ongoing pivotal phase III studies in advanced recurrent disease.
  • Sixty patients with head and neck cancer will undergo surgery at ten US sites and receive INGN 201 intraoperatively (and not postoperatively as used in the former trial) followed by a combination of chemo- and radiotherapy.
  • In September 2003, INGN 201 was granted designation as a Fast Track Drug Product development programme by the FDA for prolonging survival and delaying time to disease progression in patients with recurrent, unresectable squamous cell carcinoma of the head and neck.
  • Previously, in February 2003, INGN 201 received orphan drug designation from the FDA for head and neck cancer.
  • Phase I trials in the US for the treatment of non-small-cell lung cancer have been completed.
  • Sanofi-aventis (formerly Rhône-Poulenc Rorer Gencell) initiated phase II trials in the US, Europe and Canada for non-small-cell lung cancer.
  • Intratumoral injection of RPR/INGN 201 in patients with recurrent glioblastomas was safe and resulted in expression of the p53 protein.
  • Direct administration of RPR/INGN 201 to the lower airways of patients with bronchioalveolar cell lung carcinoma resulted in symptomatic improvement and improved lung function in some patients.
  • In November 2003, according to a Clinical Trials Agreement between the Division of Cancer Treatment and Diagnosis (DCTD) of the National Cancer Institute (NCI) and Introgen, a 6-month phase I/II study with p53 gene therapy administered in the form of an oral rinse or mouthwash for patients with oral premalignancies has been initiated.
  • This is the first trial to investigate the effect of this treatment on oral lesions that are at high risk for developing into full blown cancers.
  • In September 2006, the EMEA granted orphan drug status to INGN 201 for the treatment of LFS, following Gendux's application for the designation.
  • The company intends to provide the therapy on a compassionate use basis to qualifying patients in Europe.INGN 201 has been successfully used in the treatment of a LFS patient on a compassionate use basis under a protocol authorised by the FDA.
  • Based on these interim findings, Introgen has decided to continue making the therapy available through a compassionate use programme to eligible LFS patients who have relapsed after standard treatment as part of physician-sponsored protocols at qualifying institutions in the US.A worldwide, exclusive license to a family of US patents covering a combination therapy comprised of INGN 201 in combination with several inhibitors of epidermal growth factor receptors (EGFr) such as Erbituxtrade mark Vectibixtrade mark and Tarcevatrade mark was granted to Introgen by The University of Texas MD Anderson Cancer Center in November 2006.
  • In February 2006, Introgen exclusively licenced a broad patent (US Patent No. 6 989 375), originally issued to to the Board of Regents of The University of Texas System; the patent covers any therapeutic gene-based therapy when applied in combination with conventional cancer therapy such as radiation or chemotherapy.
  • Introgen Therapeutics was awarded a patent from the US Patent and Trademark Office in June 2005 that directly covers many of the special features of its INGN 201 molecular therapy.
  • To date, Introgen controls 30 issued patents relevant to the product covering compositions, therapeutic methods of administering the product in virtually any form, alone and in conjunction with the most widely used chemotherapeutic and radiation treatments, as well as its production, and has a large number of pending patent applications in the US and in foreign countries relating to its ADVEXIN((R)) therapy.
  • Previously, Patent No. 6,805,858 covering methods for the administration of INGN 201 to cancer patients including virtually all of those routes currently being used for adenoviral delivery was awarded.
  • This patent extends Introgen's patent coverage for its adenoviral p53 gene therapy product to the year 2021, not taking into account possible patent extensions.
  • In February 2003, the US Patent and Trademark Office issued patent No. 6,511,847, entitled Recombinant p53 Adenovirus Methods and Compositions, covering any adenoviral DNA molecule that encodes the p53 gene positioned under the control of a promoter.US patents issued in 2002 include Patent No. 6,410,010, broadly covering all adenoviral p53 compositions (including ADVEXIN((R))) that express adequate p53 in amounts sufficient to suppress the growth of or kill cancer cells in patients.
  • The patent also covers adenoviral p53, which incorporates a specific type of promoter that helps cells to express the p53 tumour suppressor gene.
  • Introgen has a number of US patents that relate to the clinical use of adenoviral p53 gene therapy in cancer as monotherapy or in combination with one or more chemotherapeutic drugs, radiation therapies or other agents that have a damaging effect on the DNA or survival of (i.e.
  • 2-methoxyestradiol, Patent No. 6,410,029) cancer cells.A patent with broad claims directed to combination therapy with the p53 gene and conventional chemotherapy or radiation was issued in China in August 2005. Patent No.
  • [MeSH-major] Adenoviridae / genetics. Genes, p53. Genetic Therapy. Neoplasms / therapy. Viral Vaccines / therapeutic use


36. Toma S, Bonelli L, Sartoris A, Mira E, Antonelli A, Beatrice F, Giordano C, Benazzo M, Caroggio A, Cavalot AL, Gandolfo S, Garozzo A, Margarino G, Schenone G, Spadini N, Sirotovà Z, Zibordi F, Balzarini F, Serafini I, Miani P, Cortesina G: 13-cis retinoic acid in head and neck cancer chemoprevention: results of a randomized trial from the Italian Head and Neck Chemoprevention Study Group. Oncol Rep; 2004 Jun;11(6):1297-305
Hazardous Substances Data Bank. 13-CIS-RETINOIC ACID .

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] 13-cis retinoic acid in head and neck cancer chemoprevention: results of a randomized trial from the Italian Head and Neck Chemoprevention Study Group.
  • Patients with squamous cell carcinoma of the head and neck (HNSCC) after being treated radically remain at high risk for both recurrent and second primary tumours.
  • 13-cis retinoic acid (13-cRA) was demonstrated to reverse pre-malignant lesions of the oral cavity and to reduce the incidence of second primary tumours in patients treated radically for HNSCC.
  • From February 1992 to January 1996, 267 patients were randomized: 126 were allocated to the control group, 126 were randomized to receive 13-cRA at a dose of 0.5 mg/kg per day per os and 15 patients have been assigned to the group of 13-cRA plus interferon alpha2a (IFN-alpha2a) at a dose of 3,000,000 UI 3 times a week (randomization in this arm interrupted due to administrative financial problems).
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Carcinoma, Squamous Cell / drug therapy. Head and Neck Neoplasms / drug therapy. Interferon-alpha / therapeutic use. Isotretinoin / therapeutic use
  • [MeSH-minor] Adult. Aged. Chemoprevention. Combined Modality Therapy. Female. Follow-Up Studies. Humans. Male. Middle Aged. Neoplasm Staging. Recombinant Proteins. Survival Analysis

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  • (PMID = 15138569.001).
  • [ISSN] 1021-335X
  • [Journal-full-title] Oncology reports
  • [ISO-abbreviation] Oncol. Rep.
  • [Language] eng
  • [Publication-type] Clinical Trial; Comparative Study; Journal Article; Multicenter Study; Randomized Controlled Trial
  • [Publication-country] Greece
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Interferon-alpha; 0 / Recombinant Proteins; 76543-88-9 / interferon alfa-2a; EH28UP18IF / Isotretinoin
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37. Biel MA: Photodynamic therapy of head and neck cancers. Methods Mol Biol; 2010;635:281-93
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Photodynamic therapy of head and neck cancers.
  • These patients include a mixture of presentations including primary, recurrent, and metastatic lesions.
  • The predominant histology is squamous cell carcinoma, but other histologies treated include mucosal melanoma, Kaposi's sarcoma, adenocarcinoma, metastatic breast carcinoma, and adenoid cystic carcinoma.
  • Several multi-institutional phase II clinical trials evaluating PDT treatment of head and neck cancers have demonstrated the efficacy of this minimally invasive therapy in the treatment of early oropharyngeal primary and recurrent cancers as well as the palliative treatment of refractory head and neck cancers.
  • Patients with early stage cancers or early recurrences in the oral cavity and larynx (Cis, T1, T2) tend to have an excellent response to PDT.
  • Of 518 patients treated with Cis, T1, or T2 cancers of the oral cavity, larynx, pharynx, and nasopharynx, 462 (89.1%) obtained a complete clinical response after one PDT treatment.
  • Photodynamic therapy is as effective as conventional therapies for the treatment of early (Cis, T1, T2) squamous cell cancers of the head and neck.
  • It is also a promising therapy to be used in association with surgery to increase tumor-free margins and therefore increase cure rates.
  • [MeSH-major] Head and Neck Neoplasms / drug therapy. Photochemotherapy
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Female. Humans. Male. Middle Aged. Randomized Controlled Trials as Topic. Treatment Outcome. Young Adult

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  • (PMID = 20552353.001).
  • [ISSN] 1940-6029
  • [Journal-full-title] Methods in molecular biology (Clifton, N.J.)
  • [ISO-abbreviation] Methods Mol. Biol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
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38. Allewelt M, Lode H: [Diagnosis and therapy of abscess forming pneumonia]. Ther Umsch; 2001 Oct;58(10):599-603
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] [Diagnosis and therapy of abscess forming pneumonia].
  • [Transliterated title] Diagnostik und Therapie abszedierender Pneumonien.
  • Differential diagnosis includes bronchial neoplasms, either as necrotizing carcinoma or as the cause of poststenotic cavernous pneumonia, other infectious diseases like tuberculosis, Pneumocystis carinii pneumonia or endocarditis with septic metastases, and lung artery embolism or vasculitis (M. Wegener).
  • Since anaerobic bacteria resemble ubiquitous commensals of the oral cavity, sputum is of no use in anaerobic culture.
  • Principal therapeutic strategy is antibiotic therapy for an extended period, usually four weeks to four months, unless radiologic changes and as well laboratory as clinical indicators of infection are completely resolved.
  • Provided that antibiotics are prescribed for a sufficient period of time and patients' compliance is ensured, surgical procedures are limited to a negligible number of complications, e.g. recurrent severe hemoptysis, empyema or broncho-pleural fistula.
  • [MeSH-minor] Diagnosis, Differential. Drug Therapy, Combination / therapeutic use. Humans. Microbial Sensitivity Tests. Penicillin G / therapeutic use

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  • (PMID = 11695090.001).
  • [ISSN] 0040-5930
  • [Journal-full-title] Therapeutische Umschau. Revue thérapeutique
  • [ISO-abbreviation] Ther Umsch
  • [Language] ger
  • [Publication-type] English Abstract; Journal Article
  • [Publication-country] Switzerland
  • [Chemical-registry-number] Q42T66VG0C / Penicillin G
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