A phase II study of irinotecan alternated with a weekly schedule of oxaliplatin, high-dose leucovorin and 48-hour infusion 5-fluorouracil in patients with advanced colorectal cancer.

Objectives: To evaluate the safety and efficacy of irinotecan (CPT-11) alternated with a weekly treatment for 4 weeks of oxaliplatin (L-OHP), high-dose leucovorin (LV) and a 48-hour 5-fluorouracil infusion (5-FU48h) as firstline chemotherapy for patients with advanced colorectal cancer (ACC). Patients and Methods: Previously untreated patients with ACC received chemotherapy consisting of a weekly treatment for 4 weeks of L-OHP ( 65 mg/m(2)), high-dose LV ( 150 mg/m(2)) followed by a 5-FU48h infusion ( 2,300 or 1,800 mg/m(2)) alternated with CPT-11 ( 350 mg/m(2)). A cycle was to be performed every 8 weeks. Treatment was continued up to tolerance, disease progression or patient refusal. Forty consecutive patients with measurable ACC, aged 26 - 70, performance status less than or equal to 2, entered our study. Results: Six complete and 17 partial responses were observed ( overall response rate, 57.5%; 95% confidence interval, CI: 38.8 - 71.1%); an additional 35% of the patients had stable disease. The median duration of response was 10.9 months ( range, 6.5 - 30+ months). The median time to progression and the median overall survival time were 11.4 ( 95% CI: 10.4-12.3) and 20.3 ( 95% CI: 16.4 - 23.7) months, respectively. At the median follow-up period of 24 months, 17 patients (42.5%) are still alive. After a median number of 4 cycles, one toxic death occurred. The incidence of grade 3 - 4 toxicity per patient in any cycle was: stomatitis 7.5%, nausea/ vomiting 2.5% and diarrhea 45% for the infusional part, neutropenia 37.5%, anemia 2.5%, thrombocytopenia 5%, alopecia 5% and diarrhea 10% for the CPT-11 part of the regimen. Gastrointestinal toxicity was different according to the dose of 5-FU. Serious adverse events occurred most frequently when 5-FU was given at a dose of 2,300 mg/m(2) with a high incidence of grade 3 - 4 diarrhea (72.2%) and stomatitis (16.6%), and led to dose reduction of 5-FU in 13 of 18 patients ( 72.2%). For 22 patients who started 5-FU at a dose of 1,800 mg/m(2), a dose reduction of 5-FU was necessary only 5 times (22.7%). No patient discontinued treatment because of severe neurotoxicity. Conclusions: The activity of our alternating regimen of L-OHP/LV/5-FU48h and CPT-11 for not previously treated ACC patients is counterbalanced by a high toxicity and a inconvenient schedule. Copyright (C) 2004 S. Karger AG, Basel.