Safety Verification Trials of mFOLFIRI and Sequential IRIS + Bevacizumab as First- or Second-Line Therapies for Metastatic Colorectal Cancer in Japanese Patients

Abstract

Objective: S-1 is effective in sequential combination with irinotecan (IRIS) in treating metastatic colorectal cancer. We conducted a randomized phase II trial of modified leucovorin, fluorouracil and irinotecan (mFOLFIRI) + bevacizumab and sequential IRIS + bevacizumab as first- or second-line therapies. Methods: Sixty metastatic colorectal cancer patients were randomly assigned to receive mFOLFIRI + bevacizumab or sequential IRIS + bevacizumab (7.5 mg/kg of bevacizumab and 150 mg/m² of irinitecan, and 80 mg/m²/day of S-1 orally from day 3 until day 16 as a 3-week course). The primary endpoint was the safety of each method until week 12, with the secondary endpoint being the comparison of the safety and efficacy of the two methods. Results: The safety of the two treatments was comparable, except that G3 anorexia and diarrhoea were less frequent with sequential IRIS + bevacizumab. The overall response rate was 62% [95% confidence interval (CI) 40.1–79.8] versus 72% (95% CI 50.6–86.2), and progression-free survival was 324 days (95% CI 247–475) versus 345 days (95% CI 312–594) with mFOLFIRI + bevacizumab versus IRIS + bevacizumab, respectively. Conclusion: Sequential IRIS + bevacizumab is a safe and effective method of systemic chemotherapy against metastatic colorectal cancer and is compatible with mFOLFIRI + bevacizumab.