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 (VOICE trial)

Abstract

Background: In the rst-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 e cacy and safety of combination therapy with ve-cycle CAPOX (capecitabine plus oxaliplatin) plus bevacizumab, followed by ve-cycle maintenance therapy with capecitabine plus bevacizumab and reintroduction of CAPOX plus bevacizumab for ve cycles, with a preplanned oxaliplatin intermittent strategy in mCRC.Methods: Patients with untreated mCRC were administered CAPOX [oxaliplatin 130 mg/m 2 and capecitabine (2000 mg/m 2 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 ve cycles, maintenance treatment without oxaliplatin for ve cycles, and CAPOX + bevacizumab reintroduction for ve cycles or upon tumor progression. The primary endpoint was progressionfree 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 ful lled the inclusion criteria were enrolled in the evaluation of e cacy and safety. The relative dose intensity and the cumulative dose of oxaliplatin during the overall treatment period were 649.1 mg/m 2 and 1132.5 mg, respectively. Median PFS was 14.1 months (95% con dence 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 vecycle induction therapy, ve-cycle maintenance therapy with capecitabine plus bevacizumab, and ve-cycle reintroduction therapy consisting of CAPOX plus bevacizumab is safe and effective for mCRC patients.

Resource Oriented Decision Making for Treatment of Metastatic Colorectal Cancer (mCRC) in a Lower-Middle Income Country: Egyptian Foundation of Medical Sciences (EFMS) Consensus Recommendations 2020

“…In non-restricted resources, the panel adopted the currently available treatment options (Capecitabine/bevacizumab continued till disease progression or unacceptable toxicity) based on efficacy and safety data reported in AVEX trial in elderly patients above 70 years old not candidates for intensified therapy. 64,65 In patients receiving CAPOX-bevacizumab as induction therapy, de-escalation of chemotherapy and maintenance with CAP/Beva is recommended. 64 Sector 4: Systemic Treatment in the Second Line and Beyond One of the most challenging clinical situations in restricted resources setting is the management of patients progressing on prior line of treatment.…”