A multicenter phase II trial of preoperative chemoradiotherapy with S-1 plus oxaliplatin and bevacizumab for locally advanced rectal cancer



We clarified the safety and efficacy of preoperative chemoradiotherapy for locally advanced rectal cancer using a multidrug regimen (S-1 + oxaliplatin + bevacizumab).


This multicenter phase II trial involved 47 patients with locally advanced rectal cancer. All patients received S-1 orally (80 mg/m2/day on days 1–5, 8–12, 15–19, and 22–26) and infusions of oxaliplatin (50 mg/m2 on days 1, 8, 15, and 22) and bevacizumab (5 mg/kg on days 1 and 15). The total radiation dose was 40 Gy delivered in daily fractions of 2 Gy via the four-field technique. The primary endpoint was the pathological complete response rate. The secondary endpoints were safety (incidence of adverse events) and clinical response, relapse-free survival, overall survival, local recurrence, R0 resection, downstaging, and treatment completion rates.


All 47 patients received chemoradiotherapy, and 44 patients underwent curative resection. Two patients refused surgery and selected a watch-and-wait strategy. The pathological complete response rate was 18.2% in patients who underwent curative resection. The clinical response rate was 91.3% in 46 patients. Concerning hematotoxicity, there was one grade 4 adverse event (2.1%) and seven grade 3 events (14.9%). Diarrhea was the most frequent non-hematotoxic event, and the grade 3 event rate was 25.5%.


Although preoperative chemoradiotherapy for patients with locally advanced rectal cancer using the S-1 + oxaliplatin + bevacizumab regimen did not achieve the expected pathological complete response rate, this regimen led to an improved clinical response rate.

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Special thanks are given to all patients and involved institutions and investigators. Other participating institutions were Yoshinogawa Medical Center (Tokushima, Japan), National Hospital Organization Kochi National Hospital (Kochi, Japan), and Takamatsu Municipal Hospital (Kagawa, Japan). We thank Joe Barber Jr., PhD, and Jane Charbonneau, DVM, from Edanz Group (https://en-author-services.edanz.com/ac) for editing a draft of this manuscript.

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All authors contributed to the study conception and design. All authors approved the final manuscript.

Corresponding author

Correspondence to Jun Higashijima.

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Conflict of interest

Mitsuo Shimada has received commercial research grants from Taiho Pharmaceutical Co., Ltd., Yakult Honsha Co., Ltd., and Chugai Pharmaceutical Co., Ltd. All other authors have no conflicts of interest.

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Higashijima, J., Tokunaga, T., Yoshimoto, T. et al. A multicenter phase II trial of preoperative chemoradiotherapy with S-1 plus oxaliplatin and bevacizumab for locally advanced rectal cancer. Int J Clin Oncol (2021). https://doi.org/10.1007/s10147-021-01868-1

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  • Rectal cancer
  • Preoperative chemoradiotherapy
  • S-1
  • Oxaliplatin
  • Bevacizumab