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

作者：Ishihara Soichiro; Matsusaka Satoshi; Kondo Keisaku; Horie Hisanaga; Uehara Keisuke; Oguchi Masahiko; Murofushi Keiko; Ueno Masashi; Mizunuma Nobuyuki; Shinbo Taijyu; Kato Daiki; Okuda Junji; Hashiguchi Yojiro; Nakazawa Masanori; Sunami Eiji; Kawai Kazushige; Yamashita Hideomi; Okada Tohru; Ishikawa Yuichi; Nakajima Toshifusa; Watanabe Toshiaki^*

来源：Radiation Oncology, 2015, 10(1): 24.

DOI：10.1186/s13014-015-0333-8

• Rectal cancer
• Chemoradiotherapy
• Phase I study
• Oxaliplatin
• S-1

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/m(2)/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/m(2)/week to three patients. The dose was then increased in a stepwise fashion to 50 mg/m(2)/week and the highest dose level of 60 mg/m(2)/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/m(2)/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/m(2) of S-1 5 days per week plus 60 mg/m(2) 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.

• 出版日期2015-1-23
• 单位中国医学科学院肿瘤医院