Neo-adjuvant FOLFIRINOX in borderline-resectable/locally advanced pancreatic adenocarcinoma: An updated analysis
Authors: S. Temraz, M. Salim Hammoud, M. Zorkot, W. Albonji, H. Dbouk, F. Farhat, M. Charafeddine, D. Mukherji, A. Shamseddine
Journal: Annals of Oncology (2018)

Introduction: Trials examining FOLFIRINOX (5-fluorouracil, oxaliplatin, irinotecan, and leucovorin) significantly improved the response rate and median survival in patients with locally advanced/borderline resectable pancreatic cancer and showed promising results for neoadjuvant use. There is currently limited experience with neoadjuvant FOLFIRINOX (nFOLFIRINOX) in borderline resectable and locally advanced pancreatic cancer. Methods: This is a prospective cohort study launched at the American University of Beirut Medical Center (AUBMC) and Hammoud Hospital University Medical Center (HHUMC), between November 2013 and February 2018. Forty one patients confirmed to have borderline resectable or locally advanced pancreatic adenocarcinomas were enrolled and received nFOLFIRINOX therapy. Our primary outcome was to assess the conversion of the tumor to a surgically resectable disease. The secondary outcomes were progression free survival (PFS) and overall survival (OS). Results: The total number of patients was 41, with a mean age at diagnosis 63 years; 25 (61%) were males and 16 (39%) were females. Locally advanced unresectable cases were 27 (65.9%) while borderline resectable cases were 14 (34.1%). The tumor was located in the head 17 (41.4%), body 14 (34.1%), and tail 10 (24.4%) in decreasing order. The median number of completed cycles was 10.Upon receiving nFOLFIRINOX, 7 (17.1%) had a stable disease, yet 11 (26.8%) had progression of the disease, and 3 patients (7.3%) still didn't reach the time of initial assessment. 20 (48.8%) patients showed partial response to treatment, among which 40% (8/20) underwent surgical resection of the pancreatic tumor and 40% (8/20) received stereotactic body radiation therapy (SBRT).Therefore, the percentage of patients converted to a resectable state was 19.5% (8/41). Our study sample had a median progression free survival (PFS) of 12 months and a median overall survival (OS) of 21 months. Patients who underwent surgical resection had an improved PFS (p value =0.029) and OS (p value = 0.043). The PFS at 12 months was 85.7% in patients who underwent surgical resection compared to 30.1% in those who did not while the PFS at 24 months was 57.1% compared to 22.6%. As for the OS, it was not obtained at 12 months for patients who had surgical resection but was 67.1% compared to 26.1% in patients who didn't undergo surgery at 24 months. Dose modifications were applied to 15 (36.6%) cases due to FOLFIRINOX adverse effects with the most dose limiting one being grade III neuropathy in 8 (19.5%) of cases. Conclusion: Our study supports that FOLFIRINOX administered in the neoadjuvant setting aids in enhancing conversion to resectability as surgical resection offers the best possibility for cure in patients with pancreatic cancer. It also shows beneficial effects on the PFS and OS in borderline resectable/unresectable pancreatic cancer patients. The protocol was well tolerated with mild increase in adverse events noted.