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)

• Published in: International journal of colorectal disease 2021-12, Vol.36 (12), p.2637-2647
• Main Authors: Kosugi, Chihiro, Koda, Keiji, Denda, Tadamichi, Ishibashi, Keiichiro, Ishida, Hideyuki, Seike, Kazuhiro, Sakata, Haruhito, Yanagisawa, Shinji, Miyazaki, Akinari, Takayama, Wataru, Koike, Naoto, Shimizu, Hiroaki, Matsubara, Hisahiro
• Format: Article
• Language: English
• Subjects: Bevacizumab; Cancer patients; Care and treatment; Clinical trials; Colorectal cancer; Colorectal carcinoma; Diarrhea; Gastroenterology; Hepatology; Hypersensitivity; Induction therapy; Internal Medicine; Medicine; Medicine & Public Health; Metastases; Metastasis; Monoclonal antibodies; Neutropenia; Original Article; Oxaliplatin; Patients; Peripheral neuropathy; Proctology; Reintroduction; Safety; Surgery; Survival; Targeted cancer therapy; Thromboembolism; Tumors
• ISSN: 0179-1958; 1432-1262
• DOI: 10.1007/s00384-021-03995-7

Purpose 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 intermittent oxaliplatin strategy in metastatic colorectal cancer (mCRC). Methods Patients with untreated mCRC were administered CAPOX (130 mg/m 2 oxaliplatin on day 1, 2000 mg/m 2 /day capecitabine on days 1–14, every 21 days) + 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. 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, peripheral sensory neuropathy, 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 UMIN ID: 000,005,732, date of registration: June 7, 2011.  https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000006695