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Cancer Chemotherapy and Pharmacology

, Volume 81, Issue 6, pp 1035–1041 | Cite as

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

  • Chu Matsuda
  • Michitaka Honda
  • Chihiro Tanaka
  • Ken Kondo
  • Takao Takahashi
  • Chihiro Kosugi
  • Yukihiko Tokunaga
  • Hiroyoshi Takemoto
  • Ho Min Kim
  • Junichi Sakamoto
  • Koji Oba
  • Hideyuki Mishima
Original Article

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.

Keywords

Metastatic colorectal carcinoma Alternate-day administration S-1 Second-line 

Notes

Funding

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

Compliance with ethical standards

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.

Informed consent

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

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Chu Matsuda
    • 1
  • Michitaka Honda
    • 2
  • Chihiro Tanaka
    • 3
  • Ken Kondo
    • 4
  • Takao Takahashi
    • 5
  • Chihiro Kosugi
    • 6
  • Yukihiko Tokunaga
    • 7
  • Hiroyoshi Takemoto
    • 8
  • Ho Min Kim
    • 9
  • Junichi Sakamoto
    • 10
  • Koji Oba
    • 11
  • Hideyuki Mishima
    • 12
  1. 1.Department of Gastroenterological Surgery, Graduate School of MedicineOsaka UniversityOsakaJapan
  2. 2.Department of Disaster and Comprehensive MedicineFukushima Medical UniversityFukushimaJapan
  3. 3.Gifu Prefectural General Medical CenterGifuJapan
  4. 4.Nagoya Medical CenterNagoyaJapan
  5. 5.Department of Surgical Oncology, Graduate School of MedicineGifu UniversityGifuJapan
  6. 6.Teikyo University Chiba Medical CenterChibaJapan
  7. 7.Kyoto Japan Post HospitalKyotoJapan
  8. 8.Department of SurgeryKinki Central HospitalOsakaJapan
  9. 9.Department of SurgeryRinku General Medical CenterIzumisanoJapan
  10. 10.Tokai Central HospitalKagamigaharaJapan
  11. 11.Department of Biostatistics, School of Public HealthUniversity of TokyoTokyoJapan
  12. 12.Cancer CenterAichi Medical UniversityAichiJapan

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