Intraperitoneal and Intravenous Paclitaxel Plus S-1 for Gastric Cancer With Peritoneal Metastasis: A Phase 3 Randomized Clinical Trial.

Whether intraperitoneal paclitaxel, which achieves high drug concentrations in the peritoneal cavity, can improve survival has not been established in a phase 3 randomized clinical trial.

腹腔内注射紫杉醇能够在腹膜腔内达到高药物浓度，但其是否能够改善生存尚未在III期随机临床试验中得到证实。

Background

To determine whether adding intraperitoneal paclitaxel to intravenous paclitaxel plus S-1 improves overall survivalin gastric cancer with peritoneal metastasis.

确定腹腔内紫杉醇联合静脉注射紫杉醇加S-1是否能改善伴有腹膜转移的胃癌患者的总生存期。

DESIGN, SETTING, AND PARTICIPANTS: This multicenter, open-label, randomized phase 3 superiority clinical trial (DRAGON-01) was conducted in 9 hospitals in China.

设计、环境和参与者：这项多中心、开放标签、随机第三阶段优势临床试验（DRAGON-01）在中国的9家医院进行。

Enrollment went from May 2017 to March 2022, and the data cutoff was March 11, 2025.

招募工作从2017年5月开始，至2022年3月结束，数据截止日期为2025年3月11日。

The trial included adults with gastric adenocarcinoma and laparoscopically confirmed peritoneal metastasis without extraperitoneal metastases or prior systemic therapy.

该试验包括了经腹腔镜确诊的胃腺癌成人患者，且这些患者有腹膜转移但无腹膜外转移或既往系统治疗史。

Methods

The IP group received paclitaxel, 50 mg/m2, intravenously plus 20 mg/m2, intraperitoneally on days 1 and 8 of each 21-day cycle, with oral S-1, 80 mg/m2, once per day on days 1 to 14.

IP组在每个21天周期的第1天和第8天静脉注射50 mg/m2的紫杉醇，同时腹腔内注射20 mg/m2的紫杉醇，以及在第1天至第14天每天口服80 mg/m2的S-1。

The PS group received paclitaxel, 70 mg/m2, intravenously on days 1 and 8, with S-1 80, mg/m2, once per day on days 1 to 14.

PS组在每个21天周期的第1天和第8天静脉注射70 mg/m2的紫杉醇，以及在第1天至第14天每天口服80 mg/m2的S-1。

main_outcomes_and_measures

The primary end point was overall survival. Secondary end points included progression-free survivaland safety.

主要终点是总生存。次要终点包括无进展生存和安全性。

Results

Among 222 treated patients (median [IQR] age, 59 [48-66] years; 104 [46.8%] female individuals and 118 [53.2%] male individuals), median (IQR) follow-up was 72.2 (50.8-80.2) months.

在222名接受治疗的患者中（中位年龄[四分位数间距]为59[48-66]岁；104名[46.8%]为女性，118名[53.2%]为男性），中位随访时间为72.2（50.8-80.2）个月。

Of 246 who were assessed, 238 (96.7%) were randomized 2:1 to receive intraperitoneal and intravenous paclitaxel plus oral S-1 (IP group) or intravenous paclitaxel plus S-1 (PS group); 222 (90.2%) received treatment (primary analysis).

在被评估的246名患者中，有238名（96.7%）按照2:1的比例被随机分配接受腹腔内和静脉注射紫杉醇加口服S-1（IP组）或仅静脉注射紫杉醇加S-1（PS组）；222名（90.2%）接受了治疗（主要分析）。

Median overall survivalwas 19.4 months (95% CI, 17.1-22.9) in the IP group and 13.9 months (95% CI, 10.3-16.1) in the PS group (hazard ratio, 0.67; 95% CI, 0.50-0.90; P = .01).

IP组的中位总生存期为19.4个月（95%置信区间，17.1-22.9），而PS组为13.9个月（95%置信区间，10.3-16.1）（风险比，0.67；95%置信区间，0.50-0.90；P = .01）。

Median progression-free survivalwas 11.2 months (95% CI, 9.3-14.0) vs 7.2 months (95% CI, 5.7-11.6) (hazard ratio, 0.72; 95% CI, 0.54-0.96).

中位无进展生存期为11.2个月（95% 置信区间，9.3-14.0）对比7.2个月（95% 置信区间，5.7-11.6）（风险比，0.72；95% 置信区间，0.54-0.96）。

Grade 3 or 4 adverse events occurred in 57 (38.5%) in the IP group and 31 (41.9%) in the PS group; no treatment-related deaths occurred.

IP组中有57例（38.5%）和PS组中有31例（41.9%）发生了3级或4级不良事件；未发生与治疗相关的死亡事件。

conclusions_and_relevance

The results of this randomized clinical trial of patients with gastric cancer with peritoneal metastasis suggest that adding intraperitoneal paclitaxel to intravenous paclitaxel plus S-1 significantly improved overall survivalwithout increasing severe toxic effects, potentially providing an encouraging signal for IP therapy in first-line treatment of gastric cancer with peritoneal metastasis.

这项针对伴有腹膜转移的胃癌患者的随机临床试验结果表明，将腹腔内紫杉醇加入静脉注射紫杉醇加S-1治疗中显著提高了总生存率，且未增加严重毒性反应，这可能为腹腔内治疗在胃癌伴有腹膜转移的一线治疗中提供了令人鼓舞的信号。

trial_registration

chictr.org.cn Identifier: ChiCTR-IIR-16009802.

chictr.org.cn 标识符：ChiCTR-IIR-16009802。