Phase I study of preoperative chemoradiotherapy with sequential oxaliplatin and irinotecan with S‑1 for locally advanced rectal cancer

Fujikawa,Hiroyuki; Toiyama,Yuji; Inoue,Yasuhiro; Omura,Yusuke; Ide,Shozo; Kitajima,Takahito; Yasuda,Hiromi; Okugawa,Yoshinaga; Okita,Yoshiki; Yoshiyama,Shigeyuki; Hiro,Junichiro; Kobayashi,Minako; Ohi,Masaki; Araki,Toshimitsu; Kusunoki,Masato

doi:10.3892/ol.2019.10028

Phase I study of preoperative chemoradiotherapy with sequential oxaliplatin and irinotecan with S‑1 for locally advanced rectal cancer

Authors:
- Hiroyuki Fujikawa
- Yuji Toiyama
- Yasuhiro Inoue
- Yusuke Omura
- Shozo Ide
- Takahito Kitajima
- Hiromi Yasuda
- Yoshinaga Okugawa
- Yoshiki Okita
- Shigeyuki Yoshiyama
- Junichiro Hiro
- Minako Kobayashi
- Masaki Ohi
- Toshimitsu Araki
- Masato Kusunoki
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Affiliations: Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Tsu, Mie 514‑8507, Japan
Published online on: February 8, 2019 https://doi.org/10.3892/ol.2019.10028
Pages: 3930-3936

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Abstract

The present study designed a novel preoperative chemoradiotherapy (CRT) with sequential oxaliplatin and irinotecan with S‑1 for locally advanced rectal cancer (LARC). This phase I study evaluated the maximum tolerated dose and recommended dose (RD) of oxaliplatin following irinotecan with S‑1. Patients with clinical stage T3 or 4 or involvement of the regional nodes and no evidence of distant metastases were treated with fixed doses of S‑1 (80 mg/m2/day) on days 1‑5, 8‑12, 15‑19, 22‑27 and 29‑33, and irinotecan (40 mg/m2/day) on days 1 and 8, followed by oxaliplatin on days 22 and 29. The dose of oxaliplatin was initially 40 mg/m2 (level 1) with a predefined dose escalation schedule. The radiation dose was 1.8 Gy/fraction to a total dose of 45 Gy. A total of 9 patients were enrolled in the present study and 7 patients completely received CRT with this study protocol. The maximum tolerated dose for oxaliplatin was 50 mg/m2 (level 2). Three of four patients experienced dose‑limiting toxicity (grade 3 diarrhea) in oxaliplatin phase of level 2 dose. The RD of oxaliplatin was 40 mg/m2 (level 1 dose). In addition, 2 patients had pathological CR (28.5%). Novel preoperative CRT with sequential oxaliplatin and irinotecan with S‑1 for LARC resulted in acceptable toxicity and promising efficacy. However, the RD of oxaliplatin was lower than in previous CRT studies that combined oxaliplatin with S‑1. To administer higher oxaliplatin, we have planned a phase I trial of preoperative CRT with sequential oxaliplatin followed by irinotecan with S‑1 for LARC.

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