title: Irinotecan plus 5-FU and leucovorin in advanced colorectal cancer: North American trials.
abstract: But fluorouracil (5-FU) and irinotecan (CPT-11 [Camptosar]) have shown activity in metastatic colorectal cancer and are approved for its treatment in the United States. Preclinical experiments in cell cultures and human tumor xenografts have indicated potential synergy when irinotecan is combined with 5-FU and leucovorin. The synergy appears to be sequence-dependent and is optimal when irinotecan exposure precedes 5-FU exposure by at least 24 hours. Four North American trials have been reported in which the three drugs were used together in either simultaneous, sequential, or alternating schedules. All three schedules showed activity in patients with metastatic colorectal cancer. The concern that diarrhea, which can be a dose-limiting toxicity with both irinotecan and 5-FU, would prevent the two drugs from being combined in reasonable doses has not proven to be a clinical issue. Phase III trials comparing the combination of the three drugs in a variety of schedules against 5-FU plus leucovorin alone are currently under way or in the planning stages.
authors.affiliation: Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Goldberg
authors.forename: C
authors.initials: C
authors.lastname: Erlichman
mesh_terms: D000931:Antidotes / Q000627:therapeutic use*; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D003967:Diarrhea / Q000139:chemically induced; D004359:Drug Therapy, Combination; D005472:Fluorouracil / Q000627:therapeutic use*; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000627:therapeutic use*; D009656:North America
chemical_list: D000931:Antidotes; D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin