Phase II Trial of Oxaliplatin/Irinotecan/5-Fluorouracil/Leucovorin for Metastatic Colorectal Cancer

BackgroundIndividually, oxaliplatin and irinotecan have substantial activity in metastatic colorectal cancer (CRC) in combination with 5-fluorouracil/leucovorin. A combination regimen using all 4 agents could potentially increase response rates in CRC.Patients and MethodsA multicenter phase II trial of oxaliplatin 85 mg/m2 on day 1, irinotecan 175 mg/m2 on day 1, 5-fluorouracil 240 mg/m2 by 90-minute infusion on days 2–5, and leucovorin 20 mg/m2 on days 2–5 of a 21-day cycle was undertaken in patients with CRC through the North Central Cancer Treatment Group. The primary endpoint was response rate, with secondary endpoints of toxicity and quality of life.ResultsOf 14 patients enrolled (13 evaluable), 3 partial responses were seen (23%; 95% confidence interval, 5%–54%), and 9 patients had stable disease (69%). Toxicity was significant, with 1 (8%) grade 5 event (diarrhea and dehydration) and 3 (23%) grade 4 events (leukopenia and diarrhea). The study was closed to further enrollment because of toxicity.ConclusionThe 4-drug regimen was extremely toxic. Future studies incorporating irinotecan- and oxaliplatin-based therapy should consider alternative schedules.