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

Irinotecan (CPT11) has established activity in the treatment of advanced colorectal cancer without cross-resistance with established 5-fluorouracil/folinic acid-based therapy. This phase II study was conducted to establish the efficacy and tolerance of combination treatment with irinotecan and 5-fluorouracil as salvage treatment for this disease. Open phase II trial of CPT11 180 mg/m2 on day 1, leucovorin 200 mg/m2 on days 1 and 2, and 5-fluorouracil 400 mg/m2 loading dose followed by 600 mg/m2 infusion on days 1 and 2. Treatment was continued until progression or limiting toxicity. Responders could proceed to surgical resection of residual disease. Thirty-nine 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 obtained stabilization of disease or minor responses (MR); of these patients, 8 with liver metastasis (7 partial response and 1 MR) underwent hepatic resection of metastases and all them obtained a complete response. The median duration of response was 14 months, and the median survival was 11 months. Hematologic 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 reported experience of a phase I study designed to establish the dose of CPT11. Efficacy in this poor prognosis group of patients is very encouraging, and the schedule is well tolerated by even previously treated patients.