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A phase II study of bevacizumab and irinotecan plus alternate-day S-1 as a second-line therapy in patients with metastatic colorectal cancer: the AIRS study

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Abstract

Background

The aim of this single-arm phase II clinical trial was to evaluate whether the alternate-day administration of S-1 plus irinotecan would reduce the incidence of severe diarrhea in comparison to consecutive-day S-1 administration (standard IRIS regimen) in second-line treatment for patients with metastatic colorectal cancer.

Methods

Patients with metastatic colorectal cancer after failure with first-line treatment of oxaliplatin and fluoropyrimidine were enrolled. Irinotecan (150 mg/m2) and bevacizumab (5 mg/kg) were given intravenously on day 1. Oral S-1 was administered on alternate days at a dose of 40–60 mg twice a day. Cycles were repeated every 2 weeks. The primary endpoint was the incidence of grade ≥ 3 diarrhea. Our hypothesis set 21% as a threshold incidence and 10% as an expected incidence from previous studies with one-sided alpha 0.05. The secondary endpoints included the relative dose intensity, progression-free survival, overall survival and other adverse events.

Results

A total of 51 patients were enrolled. The incidence of grade ≥ 3 diarrhea was 15.7% (8/51). Other common grade ≥ 3 adverse events were neutropenia, anemia, thrombocytopenia and fatigue were 13.7% (7/51), 5.9% (3/51), 2.0% (1/51) and 5.9% (3/51), respectively. The relative dose intensities of irinotecan, bevacizumab, and S-1 were 80.0, 86.8, and 77.7%, respectively. The median progression-free survival and overall survival were 8.4 months (5.8–9.8) and 17.1 months (11.8–22.3).

Conclusions

The alternate-day S-1 administration does not have significant effectiveness to reduce diarrhea in patients who received second-line treatment for metastatic colorectal cancer.

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Funding

This study fund was provided to ECRIN by Taiho Pharmaceutical Co., Ltd., under the study contract.

Author information

Author notes

  1. Chu Matsuda and Michitaka Honda equally contributed to this study.

Authors and Affiliations

  1. Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan

    Chu Matsuda

  2. Department of Disaster and Comprehensive Medicine, Fukushima Medical University, 1 Hikarigaoka, Fukushima, Fukushima, 960-1295, Japan

    Michitaka Honda

  3. Gifu Prefectural General Medical Center, Gifu, Japan

    Chihiro Tanaka

  4. Nagoya Medical Center, Nagoya, Japan

    Ken Kondo

  5. Department of Surgical Oncology, Graduate School of Medicine, Gifu University, Gifu, Japan

    Takao Takahashi

  6. Teikyo University Chiba Medical Center, Chiba, Japan

    Chihiro Kosugi

  7. Kyoto Japan Post Hospital, Kyoto, Japan

    Yukihiko Tokunaga

  8. Department of Surgery, Kinki Central Hospital, Osaka, Japan

    Hiroyoshi Takemoto

  9. Department of Surgery, Rinku General Medical Center, Izumisano, Japan

    Ho Min Kim

  10. Tokai Central Hospital, Kagamigahara, Japan

    Junichi Sakamoto

  11. Department of Biostatistics, School of Public Health, University of Tokyo, Tokyo, Japan

    Koji Oba

  12. Cancer Center, Aichi Medical University, Aichi, Japan

    Hideyuki Mishima

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  1. Chu Matsuda
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Corresponding author

Correspondence to Michitaka Honda.

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Conflict of interest

JS has received honoraria from Tsumura, Chugai Pharmaceutical, and consulting fee from Takeda Pharmaceutical. HM has received consulting fee from Takeda Pharmaceutical, Chugai Pharmaceutical, Ono Pharmaceutical and Taiho Pharmaceutical. Other authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee 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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Matsuda, C., Honda, M., Tanaka, C. et al. A phase II study of bevacizumab and irinotecan plus alternate-day S-1 as a second-line therapy in patients with metastatic colorectal cancer: the AIRS study. Cancer Chemother Pharmacol 81, 1035–1041 (2018). https://doi.org/10.1007/s00280-018-3568-x

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