CPT-11 (irinotecan) and 5-fluorouracil: a promising combination for therapy of colorectal cancer.
CPT-11 (Campto, irinotecan) is a new topoisomerase I inhibitor and one of very few new cytotoxic agents to demonstrate clinical activity in colorectal cancer since the introduction of 5-fluorouracil (5-FU) into clinical practice almost 40 years ago. Because of the unique mechanism of action of CPT-11, its proven activity in colorectal cancer, and its lack of cross-resistance with 5-FU, the combination of CPT-11 with 5-FU is a logical approach to attempt to improve on the results obtained with CPT-11 or 5-FU-based treatments alone. Various administration schedules of CPT-11/5-FU combinations have been investigated in phase I studies in Japan, the U.S. and Europe. Preliminary results indicate that concurrent administration of substantial doses of CPT-11, 5-FU and folinic acid is feasible in terms of safety. Preliminary analysis of controlled pharmacokinetic data suggests that 5-FU has no substantial effect on the metabolism of CPT-11 to its active metabolite SN-38. Major objective responses and other indicators of clinical activity have been observed with the combination in both chemotherapy-naive and pretreated patients with colorectal cancer. Studies are ongoing to define fully optimum dosage schedules of CPT-11/5-FU combinations, and some of these schedules will soon enter phase II and III clinical trials. It is hoped that such a combination will prove to be an important advance in the treatment of colorectal cancer.
Saltz
L
L
Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
Shimada
Y
Y
Khayat
D
D
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D017321:Clinical Trials, Phase I as Topic; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004334:Drug Administration Schedule; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D000077146:Irinotecan
D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin