Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomised trial

Background Irinotecan is active against colorectal cancer in patients whose disease is refractory to fluorouracil. We investigated the efficacy of the se two agents combined for first-line treatment of metastatic colorectal ca ncer. Methods 387 patients previously untreated with chemotherapy (other than adj uvant) for advanced colorectal cancer were randomly assigned open-label iri notecan plus fluorouracil and calcium folinate (irinotecan group, n=199) or fluorouracil and calcium folinate alone (no-irinotecan group, n=188). Infu sion schedules were once weekly or every 2 weeks, and were chosen by each c entre. We assessed response rates and time to progression, and also respons e duration, survival, and quality of life. Analyses were done on the intent ion-to-treat population and on evaluable patients. Findings The response rate was significantly higher in patients in the irin otecan group than in those in the no-irinotecan group (49 vs 31%, p<0.001 f or evaluable patients, 35 vs 22%, p<0.005 by intention to treat). Time to p rogression was significantly longer in the irinotecan group than in the no- irinotecan group (median 6.7 vs 4.4 months, p<0. 001), and overall survival was higher (median 17.4 vs 14.1 months, p=0.031). Some grade 3 and 4 toxic effects were significantly more frequent in the irinotecan group than in t he no-irinotecan group, but effects were predictible, reversible, non-cumul ative, and manageable. Interpretation Irinotecan combined with fluorouracil and calcium folinate w as well-tolerated and increased response rate, time to progression, and sur vival, with a later deterioration in quality of life. This combination shou ld be considered as a reference first-line treatment for metastatic colorec tal cancer.