A phase I dose escalation study of oxaliplatin plus oral S-1 and pelvic radiation in patients with locally advanced rectal cancer (SHOGUN trial)

Radiation Oncology

Toshiaki Watanabe²  Toshifusa Nakajima^1,11  Yuichi Ishikawa^1,15  Tohru Okada⁹  Hideomi Yamashita^1,12  Kazushige Kawai²  Eiji Sunami²  Masanori Nakazawa³  Yojiro Hashiguchi^1,10  Junji Okuda⁸  Daiki Kato^1,13  Taijyu Shinbo⁵  Nobuyuki Mizunuma⁷  Masashi Ueno¹  Keiko Murofushi^1,14  Masahiko Oguchi^1,14  Keisuke Uehara⁶  Hisanaga Horie⁴  Keisaku Kondo⁸  Satoshi Matsusaka⁷  Soichiro Ishihara² 

[1] Department of Gastroenterological Surgery, Cancer Institute Hospital, 3-8-31, Ariake, Koto-ku 135-8550, Tokyo, Japan;Department of Surgical Oncology, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku 113-8655, Tokyo, Japan;Department of Radiology, School of Medicine Jichi Medical University, 3311-1, Yakushiji, Shimotsuke 329-0498, Tochigi, Japan;Department of Surgery, School of Medicine Jichi Medical University, 3311-1, Yakushiji, Shimotsuke 329-0498, Tochigi, Japan;Department of Radiology, Osaka Medical College, 2-7, Daigaku-cho, Takatsuki 569-8686, Osaka, Japan;Division of Surgical Oncology, Department of Surgery, Nagoya University, 65, Tsurumai-cho, Syowa-ku, Nagoya 466-8550, Aichi, Japan;Department of Gastroenterology, Cancer Institute Hospital, 3-8-31, Ariake, Koto-ku 135-8550, Tokyo, Japan;Department of General & Gastroenterological Surgery, Osaka Medical College, 2-7, Daigaku-cho, Takatsuki 569-8686, Osaka, Japan;Department of Radiology, Nagoya University, 65, Tsurumai-cho, Syowa-ku, Nagoya 466-8560, Aichi, Japan;Department of Surgery, Teikyo University, 2-11-1, Kaga, Itabashi-ku 173-8605, Tokyo, Japan;Japan Clinical Cancer Research Organization, 7F Ginza Wing Bldg. 1-14-5, Ginza, Chuo-ku 104-0061, Tokyo, Japan;Department of Radiology, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku 113-8655, Tokyo, Japan;Department of Radiology, Teikyo University, 2-11-1, Kaga, Itabashi-ku 173-8605, Tokyo, Japan;Department of Radiation Oncology, Cancer Institute Hospital, 3-8-31, Ariake, Koto-ku 135-8550, Tokyo, Japan;Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-ku 135-8550, Tokyo, Japan

关键词: S-1;    Oxaliplatin;    Phase I study;    Chemoradiotherapy;    Rectal cancer;   

Others  :  1149848
DOI  :  10.1186/s13014-015-0333-8

 received in 2014-09-02, accepted in 2015-01-12,  发布年份 2015

【 摘 要 】

Background

The objective of this phase I study was to determine the maximum tolerated dose (MTD) and recommended dose (RD) of preoperative chemoradiotherapy (CRT) with S-1 plus oxaliplatin in patients with locally advanced rectal cancer.

Methods

Patients received radiotherapy in a total dose of 50.4 Gy in 28 fractions. Concurrent chemotherapy consisted of a fixed oral dose of S-1 (80 mg/m²/day) on days 1–5, 8–12, 22–27, and 29–33, plus escalated doses of oxaliplatin as an intravenous infusion on days 1, 8, 22, and 29. Oxaliplatin was initially given in a dose of 40 mg/m²/week to three patients. The dose was then increased in a stepwise fashion to 50 mg/m²/week and the highest dose level of 60 mg/m²/week until the MTD was attained.

Results

Thirteen patients were enrolled, and 12 received CRT. Dose-limiting toxicity (DLT) occurred in two of six patients (persistent grade 2 neutropenia, delaying oxaliplatin treatment by more than 3 days) at dose level 3; there were no grade 3 or 4 adverse events defined as DLT. The RD was 60 mg/m²/week of oxaliplatin on days 1, 8, 22, and 29. Twelve patients underwent histologically confirmed R0 resections, and two out of six patients (33%) given dose level 3 had pathological complete responses.

Conclusions

The RD for further studies is 80 mg/m² of S-1 5 days per week plus 60 mg/m² of oxaliplatin on days 1, 8, 22, and 29 and concurrent radiotherapy. Although our results are preliminary, this new regimen for neoadjuvant chemoradiotherapy is considered safe and active.

Trial registration

This trial was registered with Clinicaltrials.gov (identifier: NCT01227239 webcite).

【 授权许可】

   
2015 Ishihara et al.; licensee BioMed Central.

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