Phase II trial of neoadjuvant FOLFIRINOX and IMRT concurrent with FDR-gemcitabine in patients with borderline resectable pancreatic cancer

Abstract Background Preoperative therapy in borderline resectable pancreatic cancer (BRPC) is intended to increase R0 resection rates. An optimal approach in BRPC is yet to be defined. Methods Patients with BRPC, confirmed adenocarcinoma, performance status 1 and adequate organ function enrolled in a single-institution, phase II trial. Patients received FOLFIRINOX x 6 cycles, then radiation therapy (50 Gy in 25 fractions) concurrent with fixed-dose rate (FDR) gemcitabine (1 g/m2 over 100 minutes), followed by 2 additional gemcitabine infusions. CT scans were performed at 2-month intervals during treatment. Patients without distant disease were offered surgical exploration. The primary objective was R0 resection rate with an alternate hypothesis of 55%. Secondary objectives included median progression-free survival (PFS), median overall survival (OS), response rate and safety. Results Twenty-five patients with median age of 60 years (range, 47-77 years) enrolled from 11/2011 through 01/2017. Twenty-one (84%) completed FOLFIRINOX and 19 (76%) completed all protocol therapy. Treatment-related grade 3-4 toxicities included neutropenia (40%), nausea and vomiting (28%), diarrhea (16%) and fatigue (12%). Eighteen patients (72%) underwent laparotomy, 13 (52%) were resected (all R0). The median PFS and OS in 25 patients were 13.1 months (95% CI, 7.3 to 24.7) and 24.4 months (95% CI, 12.6 to 40.0), respectively. For resected patients, median PFS was 21.6 months (95% CI, 8.2-37.1) and OS was 37.1 months (95% CI, 15.4 – not reached). Conclusions Neoadjuvant therapy with FOLFIRINOX, followed by IMRT concurrent with (FDR)-gemcitabine in BRPC is feasible and tolerated. While the alternate hypothesis was not met, the OS of the resected cohort was favorable.