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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)

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International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

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/m2 oxaliplatin on day 1, 2000 mg/m2/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

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We thank Aki Komatsu (secretary at the SOAC Data Center at the Department of Frontier Surgery, Graduate School of Medicine, Chiba University) and Tomoko Nakabayashi (secretary at the Department of Surgery, Teikyo University Chiba Medical Center) for their data collection support, and all of the patients, their families, and medical staff. We thank Jane Charbonneau, DVM, and Melissa Crawford, PhD, from Edanz Group (https://jp.edanz.com/ac) for editing a draft of this manuscript.

Author information

Authors and Affiliations

  1. Department of Surgery, Teikyo University Chiba Medical Center, 3426-3 Anesaki, Ichihara, Chiba, 299-0111, Japan

    Chihiro Kosugi, Keiji Koda & Hiroaki Shimizu

  2. Division of Gastroenterology, Chiba Cancer Center, Chiba, Japan

    Tadamichi Denda

  3. Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University, Kawagoe, Saitama, Japan

    Keiichiro Ishibashi & Hideyuki Ishida

  4. Department of Surgery, Odawara Municipal Hospital, Odawara, Kanagawa, Japan

    Kazuhiro Seike

  5. Department of Surgery, Saisei Hospital, Hanamigawa, Chiba, Japan

    Haruhito Sakata

  6. Department of Surgery, Kimitsu Chuo Hospital, Kisarazu, Chiba, Japan

    Shinji Yanagisawa

  7. Department of Surgery, Funabashi Municipal Medical Center, Funabashi, Chiba, Japan

    Akinari Miyazaki

  8. Department of Surgery, Chiba Prefectural Sawara Hospital, Sakura, Chiba, Japan

    Wataru Takayama

  9. Department of Surgery, Seirei Sakura Citizen Hospital, Sakura, Chiba, Japan

    Naoto Koike

  10. Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan

    Hisahiro Matsubara

Authors
  1. Chihiro Kosugi
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Contributions

All authors contributed to the study conception and design. Chihiro Kosugi, Keiji Koda, Tadamichi Denda, and Hisahiro Matsubara: writing the protocol, data collection and interpretation, statistical analysis, and writing the paper. Keiichiro Ishibashi, Hideyuki Ishida, Kazuhiro Seike, Haruhito Sakata, Shinji Yanagisawa, Akinari Miyazaki, Wataru Takayama, Naoto Koike, and Hiroaki Shimizu: data collection and interpretation and writing paper. The first draft of the manuscript was written by Chihiro Kosugi, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Chihiro Kosugi.

Ethics declarations

Ethics approval

The protocol and informed consent forms were approved by the ethics committee of Teikyo University, Tokyo, Japan (reference number: 12–089). All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or research committees and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Patients provided written informed consent regarding the publication of their data.

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The authors declare no conflict of interest.

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Kosugi, C., Koda, K., Denda, T. et al. 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). Int J Colorectal Dis 36, 2637–2647 (2021). https://doi.org/10.1007/s00384-021-03995-7

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