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Randomized phase II study of tegafur–uracil/leucovorin versus tegafur–uracil/leucovorin plus oxaliplatin after curative resection of high-risk stage II/III colorectal cancer (SOAC-1101 trial)

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Abstract

Purpose

This randomized phase II trial compared tegafur–uracil/leucovorin (UFT/LV) plus oxaliplatin (TEGAFOX) to UFT/LV as adjuvant chemotherapy for patients with high-risk stage II/III colorectal cancer.

Methods

From 2010 to April 2015, 159 patients who underwent curative resection were randomly assigned to receive TEGAFOX (85 mg/m2 oxaliplatin on days 1 and 15, 300 mg/m2/day UFT and 75 mg/day LV on days 1–28, every 35 days for five cycles) or UFT/LV. The primary study endpoint was disease-free survival.

Results

The 3-year disease-free survival rate was 84.2% in the TEGAFOX arm, versus 62.1% for UFT/LV. The stratified hazard ratio for disease-free survival for TEGAFOX compared to UFT/LV was 0.338 (P < 0.01). The incidence of any-grade adverse events was significantly higher in the TEGAFOX arm (96.1%) than in the UFT/LV arm (76.6%; P < 0.01). The rates of any-grade neutropenia, thrombocytopenia, aspartate aminotransferase/alanine aminotransferase elevation, and peripheral sensory neuropathy were higher in the TEGAFOX group, whereas the incidence of grade ≥ 3 adverse events did not differ between the groups.

Conclusions

TEGAFOX is an additional adjuvant chemotherapy option for high-risk stage II/III colorectal cancer.

Trial registration

UMIN ID: 000007696, date of registration: April 10, 2012

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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) for her assistance with data collection and all of the patients, their families, and medical staff. We thank Joe Barber Jr., PhD, from Edanz Group (https://en-author-services.edanz.com/ac) for editing a draft of this manuscript.

Availability of data and material

All authors had access to the data published in this paper. Data have been uploaded to the Japan Registry of Clinical Trials online platform of the National Institute of Public Health.

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

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

    Nobuhiro Takiguchi

  3. Department of Surgery, Seikei-kai Chiba Medical Center, Chiba, Japan

    Satoru Takaishi

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

    Hideaki Miyauchi & Hisahiro Matsubara

  5. Department of Surgery, Kumagaya General Hospital, Kumagaya, Saitama, Japan

    Nobuo Hirayama

  6. Department of Surgery, Asahi General Hospital, Asahi, Chiba, Japan

    Yukihiro Nomura

  7. Department of Surgery, Japanese Red Cross Narita Hospital, Narita, Chiba, Japan

    Eisuke Kondo

  8. Biostatistics Section, Clinical Research Center, Chiba University Hospital, Chiba, Japan

    Yohei Kawasaki & Yoshihito Ozawa

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  1. Chihiro Kosugi
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Contributions

All authors contributed to the study conception and design. Chihiro Kosugi, Keiji Koda, Hideaki Miyauchi, and Hisahiro Matsubara: writing the protocol, data collection and interpretation, and writing the paper. Yohei Kawasaki and Yoshihito Ozawa: protocol writing, statistical analysis, and writing the paper. Nobuhiro Takiguchi, Satoru Takaishi, Nobuo Hirayama, Yukihiro Nomura, and Eisuke Kondo: data collection and interpretation and writing the paper. The first draft of the manuscript was written by Chihiro Kosugi, and all authors commented on previous version of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Chihiro Kosugi.

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Ethics approval

The protocol and informed consent forms were approved by the ethics committee of the Graduate school of Medicine, Chiba University (reference number: CRB3180015). All procedures performed in studies involving human participants were conducted in accordance with the ethical standards of the institutional and/or research committee and with the 1964 Declaration of Helsinki 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 publication of their data.

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The authors declare no competing interests.

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Kosugi, C., Koda, K., Takiguchi, N. et al. Randomized phase II study of tegafur–uracil/leucovorin versus tegafur–uracil/leucovorin plus oxaliplatin after curative resection of high-risk stage II/III colorectal cancer (SOAC-1101 trial). Int J Colorectal Dis 36, 1739–1749 (2021). https://doi.org/10.1007/s00384-021-03906-w

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