Multicenter phase II clinical study of the efficiency and safety of capecitabine plus intermittent oxaliplatin with bevacizumab as first-line therapy in patients with metastatic colorectal cancer: the VOICE trial

Background: In the first-line treatment of metastatic colorectal cancer (mCRC) patients with CAPOX plus bevacizumab, the optimal duration of maintenance treatment without oxaliplatin to avoid discontinuation of therapy due to peripheral sensory neuropathy (PSN) remains unknown. The aim of this phase II study was to evaluate the efficacy and safety of combination therapy with five-cycle CAPOX (capecitabine plus oxaliplatin) plus bevacizumab, followed by five-cycle maintenance therapy with capecitabine plus bevacizumab and reintroduction of CAPOX plus bevacizumab for five cycles, with a preplanned oxaliplatin intermittent strategy in mCRC.Methods: Patients with untreated mCRC were administered CAPOX [oxaliplatin 130 mg/m2 and capecitabine (2000 mg/m2 daily) as intermittent treatment for 14 days, followed by a 7-day treatment-free interval, every 3 weeks] + bevacizumab (7.5 mg/kg) every 3 weeks for five cycles, maintenance treatment without oxaliplatin for five cycles, and CAPOX + bevacizumab reintroduction for five cycles or upon tumor progression. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were the time to treatment failure (TTF), overall survival, response rate (RR), and safety.Results: Forty-seven patients who fulfilled the inclusion criteria were enrolled in the evaluation of efficacy and safety. The relative dose intensity and the cumulative dose of oxaliplatin during the overall treatment period were 649.1 mg/m2 and 1132.5 mg, respectively. Median PFS was 14.1 months (95% confidence interval [CI], 8.6–19.5), and median TTF was 12.3 months (95% CI, 10.3–14.3). The objective RRs were 51.1% (24/47) during induction therapy, 58.3% (21/36) during maintenance therapy, and 63.6% (14/22) during reintroduction therapy. The frequency of patients with neutropenia, diarrhea, PSN, venous thromboembolism, or grade ≥ 3 allergic reactions was 2.1%.Conclusion: CAPOX plus bevacizumab therapy with a preplanned intermittent oxaliplatin strategy consisting of brief five-cycle induction therapy, five-cycle maintenance therapy with capecitabine plus bevacizumab, and five-cycle reintroduction therapy consisting of CAPOX plus bevacizumab is safe and effective for mCRC patients.Trial registration: This trial was registered with the University Hospital Medical Information Network on 7 June 2011 (UMIN ID: 000005732).