Prospective phase II trial of irinotecan, 5-fluorouracil, and leucovorin in combination as salvage therapy for advanced colorectal cancer

Irinotecan (CPT11) has established activity in the treatment of advanced co lorectal cancer without cross-resistance with established 5-fluorouracil/fo linic acid-based therapy. This phase II study was conducted to establish th e efficacy and tolerance of combination treatment with irinotecan and 5-flu orouracil as salvage treatment for this disease. Open phase II trial of CPT Ii 180 mg/m(2) on day 1, leucovorin 200 mg/m(2) on days 1 and 2, and 5-flu orouracil 400 mg/m(2) loading dose followed by 600 mg/m(2) infusion on days 1 and 2. Treatment was continued until progression or limiting toxicity. R esponders could proceed to surgical resection of residual disease. Thirty-n ine patients from 2 institutions received a total of 287 cycles of therapy (median 7 cycles/patient). Eight patients achieved an objective response (7 for liver metastasis and 1 for lung metastasis), and an additional 12 obta ined stabilization of disease or minor responses (MR): of these patients, 8 with liver metastasis (7 partial response and 1 MR) underwent hepatic rese ction of metastases and all them obtained a complete response. The median d uration of response was 14 months, and the median survival was 11 months. H ematologic toxicity (neutropenia) was the most common serious side effect ( 29% of patients in 2% of cycles), but significant fever developed in only 4 patients. Grade III diarrhea was experienced in at least 1 cycle by 10% of patients. The results of this schedule compare favorably with previously r eported experience of a phase I study designed to establish the dose of CPT 11. Efficacy in this poor prognosis group of patients is very encouraging, and the schedule is well tolerated by even previously treated patients.