Irinotecan plus oxaliplatin: a promising combination for advanced colorectal cancer.
The standard treatment for advanced colorectal cancer (CRC) has been 5-fluorouracil (5-FU)-based chemotherapy. However, addition of irinotecan, a topoisomerase I inhibitor, to the combination of 5-FU and leucovorin (LV) has proven to be superior to treatment with 5-FU/LV alone in both chemonaive as well as previously treated patients. Oxaliplatin, a 1,2 diaminocyclohexane platinum compound, in combination with 5-FU and LV, has demonstrated superiority as first-line therapy over 5-FU and LV in terms of response rate and time to progression. The irinotecan/oxaliplatin combination showed synergistic activity in vitro, and the optimal dose safety profile has been explored in several phase I studies. Neutropenia and diarrhea were the dose-limiting toxicities. The recommended dose of irinotecan/oxaliplatin in every-2-week and every-3-week schedules ranged from 150-200 mg/m2 and 85 mg/m2, respectively. In the weekly schedule, the recommended doses of irinotecan/oxaliplatin were 65 mg/m2 and 60 mg/m2. Promising clinical efficacy in CRC was observed in all studies. A recent randomized phase II study revealed that the irinotecan/oxaliplatin combination has equivalent clinical activity to other 5-FU-based combinations and a manageable toxicity profile. The evaluation of irinotecan/oxaliplatin in phase III trials as well as in combination with 5-FU is ongoing.
Wasserman
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Cvitkovic & Associés Consultants, Argentina, Echeverria 1442, E.P. of 49 (1428), Buenos Aires, Argentina. e_wasserman@ciudad.com.ar
Sutherland
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Cvitkovic
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D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D002986:Clinical Trials as Topic; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004334:Drug Administration Schedule; D004357:Drug Synergism; D006801:Humans; D000077146:Irinotecan; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D016896:Treatment Outcome
D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000077146:Irinotecan; D002166:Camptothecin