Pilot study of neoadjuvant FOLFIRINOX in unresectable locally advanced (LA) pancreatic carcinoma (PC).

Abstract

324 Background: 5-flourouracil, leucovorin, irinotecan and oxaliplatin (FOLFIRINOX) is superior to gemcitabine in patients (pts) with advanced PC who have a good performance status (Conroy et al, ACCORD 11 trial, ASCO 2010). After the initial data on FOLFIRINOX were presented at ASCO 2007, we began using it off-protocol as neoadjuvant therapy for LAPC. We report our experience herein. Methods: In this retrospective series, we included pts with unresectable LAPC who received neoadjuvant FOLFIRINOX. The doses were identical to the ACCORD 11 trial, with G-CSF prophylaxis from cycle 1. The primary endpoint was R0 resection rate. Secondary endpoints were overall survival (OS), safety and tolerability. Results: Between 5/2008 and 9/2010, we treated 12 pts with LAPC with neoadjuvant FOLFIRINOX. All pts met consensus criteria for unresectability after multidisciplinary review. The median age was 57.5 years and 9/12 were men. All had ECOG PS of 0 or 1. Two pts received gemcitabine prior to FOLFIRINOX and 10 were treatment-naive. Two pts are still on therapy and 10 completed a median of 6 cycles (range 3-17) and were evaluable; 6 were felt to have converted to resectability by imaging and were taken for surgery. Four had R0 resections (40% of evaluable, 33% of all patients), 1 had R1 resection, and 1 had unresectable disease at laparotomy. To date, 2 pts have died and 10 remain alive with a Kaplan-Meier estimated median OS of 20.7 months (95% CI 18.8-22.6). All 4 pts with R0 resections are alive and disease- free. Grade 3/4 chemotherapy-related toxicities were neutropenia (17%), neutropenic fever (8%) and fatigue (17%). Common grade 1/2 toxicities were neutropenia (42%), anemia (92%), thrombocytopenia (50%), fatigue (92%), nausea (58%), diarrhea (42%) and neuropathy (33%). Two of the 6 surgical pts had significant postoperative complications - 1 with C. Difficile colitis, gastroparesis and a subhepatic collection and another with an infected pancreatic bed collection requiring percutaneous drainage 3 times. Conclusions: FOLFIRINOX is feasible as neoadjuvant therapy in patients with unresectable LAPC, with manageable toxicities. In this small series, the R0 resection rate was at least 33%. A prospective trial is warranted. No significant financial relationships to disclose.