Bulletin du cancer
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Irinotecan (CPT11), a topoisomerase I inhibitor, is a new cytotoxic agent with a broad spectrum of clinical activity. Two main schedules have been studied and produce similar activity and side-effects: the "european" one--350 mg/m2 every 21 days-, and the "japanese-north american" one where CPT11 is given at a weekly dose of 100-120 mg/m2 for 4 consecutive weeks followed by a 2 week rest period. Activity was initially characterized in advanced colorectal cancers; response rates, disease free-survival and overall survival were 11%, 7-10 months and 8-11 months in patients failing fluoropyrimidine based chemotherapy--statistically improved as compared to best supportive care and infusional fluorouracil-, and 20-30% in patients not previously treated. ⋯ Irinotecan can be combined to fluoropyrimidines, raltitrexed, cisplatin, carboplatin and oxaliplatin, to gemcitabine, etoposide, vinorelbine and taxanes with flexible schedules (weekly, every 2 weeks, every 21 days. Most of these combinations have an additive or supra additive activity. Its mechanism of action, the spectrum of activity and the acceptable risk-benefit ratio point to irinorecan as a major advance in the field of cytotoxic anticancer therapy.
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Review Practice Guideline Guideline
[Standards, options and recommendations (SOR) for clinical care of rhabdomyosarcoma (RMS) and other soft tissue sarcoma in children. Federation of the French Cancer Centers. French Society of Pediatric Oncology].
The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres and specialists from French Public Universities, General Hospitals and Private Clinics. For pediatric issues, this project is a collaboration between the FNCLCC and the French Society of Pediatric Oncology (SFOP). The main objective is the development of clinical practice guidelines to improve the quality of health care and outcomes for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. ⋯ The main recommendations for rhabdomyosarcoma management are: 1/ diagnosis is based on appropriate clinical and radiological findings; 2/ pathological and immunohistochemical studies are essential to confirm the diagnosis; 3/ surgery must be performed by an experienced surgeon. Surgery and radiotherapy must be as conservative as possible; 4/ therapeutic strategies for rhabdomyosarcoma depend on location and extends and are based on chemotherapy, surgery and radiotherapy. Inclusion of patients in SFOP, SIOP and IRS clinical trials is recommended; 5/ treatment of metastatic rhabdomyosarcoma is based on intensive chemotherapy, and surgery with or without radiotherapy; 6/ the management of non-rhabdomyosarcoma is based on the likelihood of sensitivity to chemotherapy; 7/ at the present time, there are no clear data on which to base guidelines for timing and duration of follow-up studies in these conditions.
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Treatments of advanced colorectal cancer progressing after a 5FU based chemotherapy have not been extensively studied. However, 5FU in continuous infusion, L-OHP alone or in combination with 5FU and CPT11 have proved their efficacy in terms of tumor growth control and symptomatic effect. Irinotecan only has been evaluated prospectively in phase III studies. ⋯ Both treatments were equally well tolerated. These two randomized studies have proved the efficacy of irinotecan as second line chemotherapy for colorectal cancers progressing under 5FU. Combination of irinotecan to 5FU and/or L-OHP have now to be evaluated in this situation.
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Review
[Irinotecan: various administration schedules, study of drug combinations, phase I experience].
Irinotecan (CPT11) is a synthetic camptothecin-derived DNA topoisomerase I inhibitor. Based on phase I clinical trials, several schedules have been recommended for phase I studies including 350 mg/m2 every 3 weeks in Europe, 125 mg/m2 for 4 weeks every 6 weeks in the USA, and 100 mg/m2 weekly or delayed until recovery in case of grade > 2 toxicity in Japan. The principal dose-limiting toxicities in those schedules are neutropenia and delayed diarrhea. ⋯ Those variations may be related to modifications in the hepatic metabolism of the drug that may occur in patients with hepatic dysfunction and/or in patients with concomitant medications. The understanding of the individual metabolism of the drug would help to determine individual dose adaptation. Based on synergistic preclinical interaction with several drugs, combinations of irinotecan with other cytotoxic drugs such as thymidylate synthethase inhibitors and platinum salts are currently investigated in phase I-II studies.
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As a single agent, irinotecan has demonstrated efficacy in metastatic 5FU resistant colorectal metastatic cancer. Chemotherapy with fluorouracil (5FU) plus leucovorin remains a standard in the treatment of patients with metastatic colorectal cancer. It seemed logical to test the combination of this reference treatment and the new agent. ⋯ The combinations of irinotecan and mitomycin C or oxaliplatin have given very good results with high objective response rates and good tolerance. Irinotecan plays now an important part in the treatment of metastatic colorectal cancer. This part becomes larger due to the results of the combination trials already presented which have shown strong efficacy and good tolerance.