First report of a Japanese phase I study of triplet plus bevacizumab for chemotherapy-naive metastatic colorectal cancer (J1-TRIBE study)

BackgroundThe aim of this study was to determine the recommended dose of irinotecan (CPT-11) with fixed regimen of oxaliplatin (L-OHP)/fluorouracil (5-FU)/leucovorin (LV) (FOLFOXIRI) plus bevacizumab in Japanese patients with metastatic colorectal cancer.Patients and methodsPatients received CPT-11 followed by L-OHP 85 mg/m2, LV 200 mg/m2, and 5-FU 3200 mg/m2 infused as a 48-h continuous infusion and bevacizumab 5 mg/kg, repeated every 2 weeks. A decrease of the CPT-11 dose was planned (started at level 1: CPT-11 165 mg/m2). This trial was registered with the University Hospital Medical Information Network (number UMIN000012991).ResultsSix patients were enrolled, and MTD was not reached at level 1. CPT-11 165 mg/ in combination with L-OHP 85 mg/m2, LV 200 mg/m2, 5-FU 3200 mg/m2 infused as a 48-h continuous infusion and bevacizumab 5 mg/kg could be administered with acceptable toxicity, and all patients were treated at these dose levels. The most common grade 3 or 4 toxicities were neutropenia (67%) and leukopenia (50%). No treatment death was observed. The overall response rate was 67% (95% confidence interval: 30.0-90.3 %).ConclusionThis biweekly triplet plus bevacizumab regimen was well tolerated by Japanese patients with metastatic colorectal cancer. The recommended phase II dose was determined to be the same as the standard doses for this regimen used worldwide.Micro abstractThe efficacy of the FOLFOXIRI plus bevacizumab regimen for patients with metastatic colorectal cancer has been proven in a recent phase III study. However, there is no report of the FOLFOXIRI plus bevacizumab regimen in Japanese patients, and recommended doses of this regimen for Japanese patients have not been determined. The present study demonstrates that the recommended doses of FOLFOXIRI plus bevacizumab for Japanese patients are the same as the standard doses used worldwide.