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

摘要

Abstract Background The 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 methods Patients 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). Results Six 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 %). Conclusion This 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 Abstract The 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.