Irinotecan plus fluorouracil and leucovorin for metastatic colorectal cancer.

Background: The combination of fluorouracil and leucovorin has until recent ly been standard therapy for metastatic colorectal cancer. Irinotecan prolo ngs survival in patients with colorectal cancer that is refractory to treat ment with fluorouracil and leucovorin. In a multicenter trial, we compared a combination of irinotecan, fluorouracil, and leucovorin with bolus doses of fluorouracil and leucovorin as first-line therapy for metastatic colorec tal cancer. A third group of patients received irinotecan alone. Methods: Patients were randomly assigned to receive irinotecan (125 mg per square meter of body-surface area intravenously), fluorouracil (500 mg per square meter as an intravenous bolus), and leucovorin (20 mg per square met er as an intravenous bolus) weekly for four weeks every six weeks; fluorour acil (425 mg per square meter as an intravenous bolus) and leucovorin (20 m g per square meter as an intravenous bolus) daily for five consecutive days every four weeks; or irinotecan alone (125 mg per square meter intravenous ly) weekly for four weeks every six weeks. End points included progression- free survival and overall survival. Results: Of 683 patients, 231 were assigned to receive irinotecan, fluorour acil, and leucovorin; 226 to receive fluorouracil and leucovorin; and 226 t o receive irinotecan alone. In an intention-to-treat analysis, as compared with treatment with fluorouracil and leucovorin, treatment with irinotecan, fluorouracil, and leucovorin resulted in significantly longer progression- free survival (median, 7.0 vs. 4.3 months; P = 0.004), a higher rate of con firmed response (39 percent vs. 21 percent, P<0.001), and longer overall su rvival (median, 14.8 vs. 12.6 months; P = 0.04). Results for irinotecan alo ne were similar to those for fluorouracil and leucovorin. Grade 3 (severe) diarrhea was more common during treatment with irinotecan, fluorouracil, an d leucovorin than during treatment with fluorouracil and leucovorin, but th e incidence of grade 4 (life-threatening) diarrhea was similar in the two g roups (<8 percent). Grade 3 or 4 mucositis, grade 4 neutropenia, and neutro penic fever were less frequent during treatment with irinotecan, fluorourac il, and leucovorin. Adding irinotecan to the regimen of fluorouracil and le ucovorin did not compromise the quality of life. Conclusions: Weekly treatment with irinotecan plus fluorouracil and leucovo rin is superior to a widely used regimen of fluorouracil and leucovorin for metastatic colorectal cancer in terms of progression-free survival and ove rall survival. (N Engl J Med 2000;343:905-14.) (C) 2000, Massachusetts Medi cal Society.