Oxaliplatin combined with irinotecan and 5-fluorouracil/leucovorin (OCFL) in metastatic colorectal cancer: a phase I-II study

Background: A phase I-II multicenter trial was conducted to define the maximal tolerated dose and describe the activity of an OCFL combination using oxaliplatin (OHP), irinotecan (CPT-II) and 5-fluorouracil (FU)/leucovorin (LV) in metastatic colorectal cancer (CRC). Patients and methods: CRC patients not pretreated with palliative chemotherapy, with performance status <= 1 and adequate haematological, kidney and liver function, were eligible. Treatment consisted in weekly 24-h infusion 5-FU (2300mg/m(2))/LV (30 mg) and alternating OHP (70-85 mg/m(2), days 1 and 15) and CPT-II (80-140 mg/m(2), days 8 and 22) repeated every 5 weeks. OHP and CPT-II were escalated in cohorts of three to six patients. Results: Thirty patients received a median of five cycles. Dose-limiting toxicity occurred at dose level 3, and the recommended dose was OHP 70 mg/m(2), CPT-II 100 mg/m(2), LV 30 mg and 5-FU 2300 mg/m(2)/24h. Grade >= 3 toxicities were diarrhea 23%, neutropenia 20%, fatigue 7%. and neurologic 7%. Two febrile neutropenia episodes (one fatal) were recorded. Among 28 patients with measurable disease (90%), we observed two complete and 20 partial responses: overall RR was 78% (95% CI, 59% to 92%). Median time to progression and overall survival were 9.5 and 25.4 months. respectively. Seven patients underwent liver metastases resection. Conclusion: OCFL is an overall well tolerated regimen with very high efficacy, which makes it most suitable for tumour control before surgery of metastatic disease.