Perioperative 5-Fluorouracil and Portal Vein Infusion Chemotherapy Followed by Adjuvant S-1 for Resected Pancreatic Cancer (TOSPAC-02): A Phase 2 Clinical Trial

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) exhibits a poor prognosis, even after curative resection. Portal vein infusion (PVI) chemotherapy with gemcitabine therapy for resected PDAC has been reported as effective. This study aimed to evaluate the efficacy of PVI chemotherapy followed by S-1 therapy as adjuvant chemotherapy following PDAC resection. METHODS: This multicenter phase II trial included patients with resected PDAC between February 2014 and May 2017. They received PVI chemotherapy with 5-fluorouracil (250 mg/day) and heparin (2000 IU/day) with systemic administration of mitomycin C (4 mg/day on days 6, 13, 20, and 27) and cisplatin (10 mg/day on days 7, 14, 21, and 28) for 4 weeks (PI4W) and S-1 therapy. The primary endpoint was recurrence-free survival (RFS). The secondary endpoints included overall survival (OS), incidence of adverse events, protocol completion rate, and relative dose intensity of S-1. RESULTS: A total of 50 patients were included in the final analysis. The median RFS and OS were 18.9 months (1-, 3-, and 5-year RFS rates: 63.3, 36.1, and 28.3%, respectively) and 63.9 months (1-, 3-, and 5-year OS rates: 91.9, 57.2, and 51.2%, respectively), respectively. Of the patients, 47 (94.0%) completed PI4W, 44 (88.0%) received S-1 therapy, and 29 (58.0%) completed PI4W plus S-1 therapy. The combination therapy had relatively favorable survival outcomes. Severe adverse events were less prevalent, and the treatment was well-tolerated. CONCLUSIONS: PI4W followed by S-1 therapy may benefit patients after curative resection of PDAC. Clinical trial register: The study was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000013430).