吉西他滨联合S-1新辅助化疗与直接手术治疗可切除胰腺癌的比较：随机II/III期Prep-02/JSAP05试验结果

Neoadjuvant Chemotherapy with Gemcitabine and S-1 versus Upfront Surgery for Resectable Pancreatic Cancer: Results of the Randomized Phase II/III Prep-02/JSAP05 Trial.

作者信息

Unno Michiaki, Motoi Fuyuhiko, Matsuyama Yutaka, Satoi Sohei, Toyama Hirochika, Matsumoto Ippei, Aosasa Suefumi, Shirakawa Hirofumi, Wada Keita, Fujii Tsutomu, Yoshitomi Hideyuki, Takahashi Shinichiro, Sho Masayuki, Ueno Hideki, Kosuge Tomoo

机构信息

Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan.

Department of Surgery I, Yamagata University, Faculty of Medicine, Yamagata, Japan.

出版信息

Ann Surg. 2025 Apr 16. doi: 10.1097/SLA.0000000000006730.

DOI:10.1097/SLA.0000000000006730

PMID:40235447

Abstract

OBJECTIVE

This randomized phase II/III study evaluated the superiority of neoadjuvant therapy with gemcitabine plus S-1 over upfront surgery for patients with resectable pancreatic ductal adenocarcinoma (PDAC).

SUMMARY BACKGROUND DATA

Pancreatic ductal adenocarcinoma is a leading cause of cancer mortality that urgently requires better treatment.

METHODS

Patients with resectable PDAC (without arterial abutment) were randomly assigned to upfront surgery or neoadjuvant chemotherapy with gemcitabine (1000 mg/m 2 days 1 and 8) and S-1 (40-60 mg orally twice daily, days 1-14 every 3 wk for 2 cycles). Phase II and III primary endpoints were resection rate and overall survival, respectively. UMIN Clinical Trials Registry number: UMIN000009634.

RESULTS

Patients (n=364) were enrolled and randomly allocated to upfront surgery (UPS; n=182) or neoadjuvant gemcitabine plus S-1 (NAC-GS; n=182). Patient demographics and tumor characteristics were balanced between groups. Median overall survival in the UPS and NAC-GS groups was 26.6 (95% confidence interval [CI] 21.5, 31.5) and 37.0 (95% CI 28.6, 43.3) months, respectively. The hazard ratio for mortality in the NAC-GS group compared with the UPS group was 0.73 (95% CI 0.56, 0.95; P =0.018). Median relapse-free survival in the UPS and NAC-GS groups was 11.3 (95% CI 9.41, 13.5) and 14.3 (95% CI 11.7, 17.0) months, respectively. The hazard ratio for relapse in the NAC-GS group compared with the UPS group was 0.77 (95% CI 0.61, 0.98; P =0.030).

CONCLUSION

The Prep-02/JSAP05 trial results showed that neoadjuvant chemotherapy with gemcitabine plus S-1 significantly extends survival compared with upfront surgery in patients with resectable PDAC.

摘要

目的

本随机II/III期研究评估了吉西他滨联合S-1新辅助治疗对比直接手术治疗可切除性胰腺导管腺癌（PDAC）患者的优越性。

总结背景数据

胰腺导管腺癌是癌症死亡的主要原因，迫切需要更好的治疗方法。

方法

可切除性PDAC患者（无动脉侵犯）被随机分配接受直接手术或吉西他滨（1000mg/m²，第1天和第8天）联合S-1新辅助化疗（40-60mg口服，每日2次，第1-14天，每3周1个周期，共2个周期）。II期和III期主要终点分别为切除率和总生存期。UMIN临床试验注册编号：UMIN000009634。

结果

共纳入364例患者并随机分配至直接手术组（UPS；n=182）或吉西他滨联合S-1新辅助化疗组（NAC-GS；n=182）。两组患者的人口统计学特征和肿瘤特征均衡。UPS组和NAC-GS组的中位总生存期分别为26.6个月（95%置信区间[CI]21.5，31.5）和37.0个月（95%CI 28.6，43.3）。与UPS组相比，NAC-GS组的死亡风险比为0.73（95%CI 0.56，0.95；P=0.018）。UPS组和NAC-GS组的中位无复发生存期分别为11.3个月（95%CI 9.41，13.5）和14.3个月（95%CI 11.7，17.0）。与UPS组相比，NAC-GS组的复发风险比为0.77（95%CI 0.61，0.98；P=0.030）。