Shinkai Masayuki, Imano Motohiro, Yokokawa Masaki, Tanaka Ryo, Matsuyama Jin, Shimokawa Toshio, Kawakami Hisato, Satoh Taroh, Yasuda Takushi, Furukawa Hiroshi
Department of Surgery, Faculty of Medicine, Kindai University, Osaka-Sayama, Osaka, Japan.
Department of Radiation Oncology, Faculty of Medicine, Kindai University, Osaka-Sayama, Osaka, Japan.
Ann Surg Oncol. 2025 Apr;32(4):2651-2661. doi: 10.1245/s10434-024-16845-x. Epub 2025 Jan 15.
To improve the prognosis of clinically resectable type 4 or large type 3 gastric cancer (GC), we performed a phase I/II study of neoadjuvant-radiotherapy combined with S-1 plus cisplatin.
Phase I, with a standard 3 + 3 dose-escalation design, was performed to define the recommended phase II dose. Efficacy and safety were evaluated in phase II. The three dose levels were as follows: level 0, S-1 60 mg/m on days 1-14 plus cisplatin 60 mg/m on day 1; level 1, S-1 80 mg/m on days 1-14 plus cisplatin 60 mg/m on day 1; and level 2, S-1 80 mg/m on days 1-14 and 22-35, plus cisplatin 60 mg/m on days 1 and 22. The starting dose was level 1. Radiotherapy was delivered at a total dose of 40 Gy in fractions for 4 weeks.
A total of six patients were enrolled in the phase I study. Dose-limiting toxicity was observed at level 2; level 1 was established as the recommended phase II dose. In phase II, 20 patients were enrolled from November 2012 to April 2018. Grade 3/4 leukopenia and nonhematologic adverse events occurred in 35% and 5% of the patients, respectively. In total, 19 patients underwent the protocol surgery; 2 (10.5%) achieved a pathological complete response. There were no treatment-related deaths; 3- and 5-year overall survival rates were 70.0 and 50.0%, respectively.
Neoadjuvant chemoradiotherapy with S-1 plus cisplatin is a safe and promising treatment for clinically resectable type 4 or large type 3 GC.
为改善临床可切除的4型或大型3型胃癌（GC）的预后，我们开展了一项新辅助放疗联合S-1加顺铂的I/II期研究。
I期采用标准的3+3剂量递增设计，以确定推荐的II期剂量。II期评估疗效和安全性。三个剂量水平如下：0级，第1 - 14天S-1 60mg/m²加第1天顺铂60mg/m²；1级，第1 - 14天S-1 80mg/m²加第1天顺铂60mg/m²；2级，第1 - 14天和22 - 35天S-1 80mg/m²，加第1天和第22天顺铂60mg/m²。起始剂量为1级。放疗总剂量为40Gy，分4周给予。
I期共纳入6例患者。在2级观察到剂量限制性毒性；确定1级为推荐的II期剂量。II期从2012年11月至2018年4月共纳入20例患者。35%和5%的患者分别发生3/4级白细胞减少和非血液学不良事件。共有19例患者接受了方案规定的手术；2例（10.5%）达到病理完全缓解。无治疗相关死亡；3年和5年总生存率分别为70.0%和50.0%。
S-1加顺铂的新辅助放化疗是临床可切除的4型或大型3型GC的一种安全且有前景的治疗方法。
