新辅助多西紫杉醇、奥沙利铂和 S-1 治疗大型 3 或 4 型胃癌患者（OGSG1902）：一项多中心、Ⅱ期研究方案。
Neoadjuvant docetaxel, oxaliplatin and S-1 therapy for the patients with large type 3 or type 4 gastric cancer (OGSG1902): protocol of a multi-center, phase II study.
机构信息
Department of Digestive Surgery, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama, 701-0192, Japan.
Cancer Chemotherapy Center, Osaka Medical and Pharmaceutical University, 2-7 Daigaku-machi, Takatsuki, Osaka, Japan.
出版信息
BMC Cancer. 2022 Jul 23;22(1):811. doi: 10.1186/s12885-022-09890-w.
BACKGROUND
Large type 3 and type 4 gastric cancers have extremely poor prognoses. To address this, neoadjuvant chemotherapy may be a promising approach. The phase III JCOG0501 study, conducted to confirm the superiority of neoadjuvant S-1 plus cisplatin followed by D2 gastrectomy over upfront surgery, showed no survival benefit for neoadjuvant S-1 plus cisplatin. In Korea, the PRODIGY study, which was a phase III study of neoadjuvant docetaxel plus oxaliplatin plus S-1 (DOS) followed by surgery and adjuvant S-1 versus surgery and adjuvant S-1 for gastric cancer of T2-3N+ or T4Nany, showed that progression-free survival (PFS) was significantly superior in the neoadjuvant DOS arm. Therefore, DOS therapy may be a promising candidate for preoperative chemotherapy for large type 3 or type 4 gastric cancer.
METHODS
Preoperative docetaxel 40 mg/m and oxaliplatin 100 mg/m will be intravenously administered on day1 every three weeks. S-1 will be orally administered 80 mg/m on days 1-14 of a 21-day cycle. Patients will receive three courses of treatment and gastrectomy with ≥D2 lymph node dissection. Postoperative S-1 plus docetaxel therapy (DS) will be administered according to the JACCRO GC-07 (START-2) study. The primary endpoint is the 3-year PFS rate. Secondary endpoints include PFS time, overall survival time, pathological response rate, response rate according to RECIST version1.1, proportion of completion of neoadjuvant chemotherapy, R0 resection rate, proportion of completion of surgery, proportion of completion of protocol treatment, proportion of negative conversion of CY, adverse event occurrence rate, and nutritional evaluation. The null hypothesis for the 3-year PFS rate is 45% and the expected value is 60%. The total sample size is 46 considering that the registration period and follow-up period are two and three years, respectively.
DISCUSSION
This is a prospective, multicenter, single-arm, open-label, phase II trial assessing the efficacy and safety of preoperative DOS and postoperative DS for large type 3 or type 4 gastric cancer. The results will inform future phase III trials and are expected to lead to new treatment strategies for large type 3 or type 4 gastric cancer.
TRIAL REGISTRATION
Registered with Japan Registry of Clinical Trials on October 11, 2019 ( jRCTs051190060 ).
背景
大型 3 型和 4 型胃癌预后极差。为了解决这个问题，新辅助化疗可能是一种有前途的方法。III 期 JCOG0501 研究旨在证实新辅助 S-1 联合顺铂加 D2 胃切除术优于 upfront 手术，但新辅助 S-1 联合顺铂并未显示出生存获益。在韩国，PRODIGY 研究是一项 III 期研究，评估新辅助多西紫杉醇联合奥沙利铂联合 S-1（DOS）加手术和辅助 S-1 治疗 T2-3N+或 T4Nany 期胃癌与单纯手术和辅助 S-1 治疗相比，无进展生存期（PFS）在新辅助 DOS 组显著提高。因此，DOS 治疗可能是大型 3 型或 4 型胃癌术前化疗的有前途的候选药物。
方法
新辅助治疗每 3 周静脉注射多西紫杉醇 40mg/m2和奥沙利铂 100mg/m2，第 1 天；S-1 口服，每天 80mg/m2，21 天为 1 个周期。患者将接受 3 个疗程的治疗，然后进行 D2 淋巴结清扫术。术后给予 S-1 加多西紫杉醇治疗（DS），根据 JACCRO GC-07（START-2）研究进行。主要终点是 3 年 PFS 率。次要终点包括 PFS 时间、总生存时间、病理缓解率、根据 RECIST 版本 1.1 的缓解率、新辅助化疗完成比例、R0 切除率、手术完成比例、方案治疗完成比例、CY 阴性转化率、不良事件发生率和营养评估。3 年 PFS 率的零假设为 45%，预期值为 60%。考虑到注册期和随访期分别为 2 年和 3 年，总样本量为 46。
讨论
这是一项前瞻性、多中心、单臂、开放标签、II 期研究，评估了术前 DOS 和术后 DS 治疗大型 3 型或 4 型胃癌的疗效和安全性。研究结果将为未来的 III 期试验提供信息，并有望为大型 3 型或 4 型胃癌带来新的治疗策略。
试验注册
于 2019 年 10 月 11 日在日本临床试验注册中心注册（jRCTs051190060）。
Zotero 插件