Neoadjuvant Chemotherapy With Gemcitabine and S-1 Versus Upfront Surgery for Resectable Pancreatic Cancer
Michiaki Unno, Fuyuhiko Motoi, Yutaka Matsuyama, Sohei Satoi, Hirochika Toyama, Ippei Matsumoto, Suefumi Aosasa, Hirofumi Shirakawa, Keita Wada, Tsutomu Fujii, Hideyuki Yoshitomi, Shinichiro Takahashi, Masayuki Sho, Hideki Ueno, Tomoo Kosuge
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). BACKGROUND: PDAC 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% 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). CONCLUSIONS: 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.