RANDOMIZED TRIAL OF IRINOTECAN VERSUS FLUOROURACIL BY CONTINUOUS-INFUSION AFTER FLUOROURACIL FAILURE IN PATIENTS WITH METASTATIC COLORECTAL-CANCER

Background In phase II trials, irinotecan is active in patients with a dvanced colorectal cancer, but the survival and clinical benefit of ir inotecan compared with second-line fluorouracil by continuous infusion is not known. Methods 267 patients who had failed to respond to first -line fluorouracil, or whose disease had progressed after treatment wi th first-line fluorouracil were randomly allocated irinotecan 300-350 mg/m(2) infused once every 3 weeks or fluorouracil by continuous infus ion. Treatment was given until disease progression, unacceptable toxic effects, or the patient refused to continue treatment. The primary en dpoint was survival, while progression-free survival, response rate, s ymptom-free survival, adverse events, and quality of life (QoL) were s econdary endpoints. Findings 133 patients were randomly allocated irin otecan and 134 were allocated fluorouracil by continuous infusion. Pat ients treated with irinotecan lived for Significantly longer than pati ents on fluorouracil (p=0.035). Survival at 1 year was increased from 32% in the fluorouracil group to 45% in the irinotecan group. Median s urvival was 10.8 months in the irinotecan group and 8.5 months in the fluorouracil group. Median progression-free survival was longer with i rinotecan (4.2 vs 2.9 months for irinotecan vs fluorouracil, respectiv ely; p=0.030). The median pain-free survival was 10.3 months and 8.5 m onths (p=0.06) for irinotecan and fluorouracil, respectively. Both tre atments were equally well tolerated. QoL was similar in both groups. I nterpretation Compared with fluorouracil by continuous infusion second -line irinotecan significantly improved survival in patients with adva nced colorectal cancer.