局部进展期直肠癌术前 S-1 联合奥沙利铂放化疗的多中心 II 期研究的长期结果（JACCRO CC-04：SHOGUN 试验）。

Long-term results of a multicenter phase II study of preoperative chemoradiotherapy with S-1 plus oxaliplatin for locally advanced rectal cancer (JACCRO CC-04: SHOGUN Trial).

机构信息

Department of General & Gastroenterological Surgery, Osaka Medical College, Takatsuki, Japan.

Department of Gastroenterology, Cancer Institute Hospital, Tokyo, Japan.

出版信息

Radiother Oncol. 2019 May;134:199-203. doi: 10.1016/j.radonc.2019.02.006. Epub 2019 Feb 26.

DOI:10.1016/j.radonc.2019.02.006

PMID:31005216

Abstract

PURPOSE

The study was designed to evaluate the safety and efficacy of adding oxaliplatin to py (CRT) with S-1 in patients with locally advanced rectal carcinoma (LARC). We report here the final results of the study.

PATIENTS AND METHODS

Patients with histopathologically confirmed LARC (cT3-T4, any N) were eligible. They received oral S-1 (80 mg/m/day on days 1-5, 8-12, 22-26, and 29-33) and infusional oxaliplatin (60 mg/m/day on days 1, 8, 22, 29) plus radiotherapy (1.8 Gy/day, total dose of 50.4 Gy in 28 fractions), with a chemotherapy gap in the third week of radiotherapy. Primary endpoint of the study was pathological complete response (pCR) rate. Secondary endpoints were rates of R0 resection, down-staging, cumulative 3-year local recurrence, 3-year disease-free survival (DFS), and toxicity.

RESULTS

Forty-five patients were enrolled at six centers in Japan. All patients received CRT, and 44 underwent operation. The pCR rate was 27.3% (12/44). The R0 resection rate was 95.5% (42/44). T-down-staging rate was 59.1% (26/44), and N-down staging rate was 65.9% (29/44); the combined pathological down-staging rate was 79.5% (35/44). There were no grade 4 adverse events, but 11.1% of the patients had grade 3 adverse events. Cumulative 3-year local recurrence rate was 0%. However, 13 (30.0%) patients suffered from distant metastasis, and one patient suffered from secondary esophageal cancer that was unrelated to rectal cancer. Eight patients had lung metastasis, 4 had liver metastasis, and 3 patients died of the metastatic disease. The 3-year DFS rate of the 44 patients was 67.5% (median follow-up 36.3 months), and the 3-year overall survival (OS) rate was 93.0% (median follow-up 39.6 months). The patients were then divided into the pCR (12 patients) group and non pCR (32 patients) group. The 3-year rate of DFS for each group was 91.7% and 58.1% and that of OS was 100% and 90.3%, respectively.

CONCLUSIONS

The study showed a high pCR rate with no severe toxicity, good follow-up results, and good loco-regional control. Therefore, addition of oxaliplatin to preoperative CRT with S-1 in patients with LARC might be feasible and lead to better local control than standard treatment.

摘要

目的

本研究旨在评估奥沙利铂联合 S-1 方案（CRT）在局部进展期直肠癌（LARC）患者中的安全性和有效性。我们在此报告该研究的最终结果。

患者和方法

符合组织病理学确认的 LARC（cT3-T4，任何 N）标准的患者有资格入组。他们接受口服 S-1（80mg/m 天，第 1-5 天、第 8-12 天、第 22-26 天和第 29-33 天）和静脉奥沙利铂（60mg/m 天，第 1、8、22、29 天）联合放疗（1.8Gy/天，总剂量 50.4Gy，28 个分次），在放疗的第三周有化疗间歇期。该研究的主要终点为病理完全缓解（pCR）率。次要终点为 R0 切除率、降期率、累计 3 年局部复发率、3 年无病生存率（DFS）和毒性。

结果

在日本的 6 个中心共入组了 45 例患者。所有患者均接受 CRT，其中 44 例患者接受了手术。pCR 率为 27.3%（12/44）。R0 切除率为 95.5%（42/44）。T 降期率为 59.1%（26/44），N 降期率为 65.9%（29/44）；联合病理降期率为 79.5%（35/44）。无 4 级不良事件，但 11.1%的患者发生 3 级不良事件。累计 3 年局部复发率为 0%。然而，13 例（30.0%）患者发生远处转移，1 例患者发生与直肠癌无关的继发性食管癌。8 例患者发生肺转移，4 例患者发生肝转移，3 例患者死于转移性疾病。44 例患者的 3 年 DFS 率为 67.5%（中位随访 36.3 个月），3 年总生存率（OS）率为 93.0%（中位随访 39.6 个月）。然后将患者分为 pCR（12 例）组和非 pCR（32 例）组。每组患者的 3 年 DFS 率分别为 91.7%和 58.1%，OS 率分别为 100%和 90.3%。