Background: Only 15-20% of patients with pancreatic cancer are eligible for curative surgery, and despite surgical resection and adjuvant therapy, 5 years survival of this group remains poor at 20%. Neoadjuvant studies combining gemcitabine and radiation demonstrated improved median overall survival in patients who completed therapy and their disease was resected. FOLFIRINOX is superior to gemcitabine in advanced disease (Conroy et al), however, its tolerability and efficacy in early stage disease is unknown.

Patients and Methods: Patients who presented to Indiana University Simon Cancer Center and have resectable pancreatic cancer after evaluation by a pancreatobiliary surgeon were offered to be treated on an IRB approved protocol with 2 months of FOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan 180 mg/m2, leucovorin 400 mg/m2 day 1, 5-FU 400 mg/m2 bolus followed by 2400 mg/m2 x 48 hours, peg-filgrastim 6 mg SQ day 3). Four to six weeks after completing therapy, patients underwent restaging CT scan and surgical consultation to assess for resectability. In case of suspected metastases due to rising CA 19-9 or suspicious lesions, diagnostic laparoscopy was performed first to assess for resectability. After recovery, patients received adjuvant therapy based on the treating physician’s discretion.

Results: Between June 2014 and December 2015, 26 patients with ECOG PS 0/1 were consented, of whom 22; (male/female: 14/8), median age was 65 (45-75 years), proceeded with therapy. Radiographic responses per RECIST after two months of therapy for evaluable patients were as follows: 2 with partial response, 13 with stable disease, and 1 with progressive disease. Fifteen completed preoperative therapy, and 13 underwent tumor resection. For the patients whom did not proceed to surgery the reason was (patients’ death: 2, toxicity 2 (shortly after being off study developed metastatic disease), distant metastatic disease on imaging: 1, and occult metastases found at the time of surgery: 2). Grades 3-5 toxicities per CTCAE V4.03 was (G5:2, G4: none, G3: one of each: dehydration, fatigue, neutropenia, and two with diarrhea). For the patients who died on study, one patient had significant cardiac history and had a sudden death, one patient developed treatment related complications. Of patients who had resection, 11 had R0 resection and 2 patients had R1 resection. TNM staging at resection was: Stage IIA (T3N0): 2, and stage IIB (T3N1): 11. Pathologic response using Evans criteria demonstrated minimal response (grade I) in 11 patients and moderate response (Grade IIA) in 2 patients. There was no apparent delayed surgical recovery related to neoadjuvant chemotherapy and patients who recovered, preceded to receive adjuvant therapy. DFS was evaluated for 13 patients who received surgery. The 25th percentile DFS was 52 weeks. Median OS for the entire group and for the group who had successful surgery is 65 weeks and not reached, respectively.

Conclusion: Neoadjuvant FOLFIRINOX is feasible in patients with resectable pancreatic cancer. In our small study, objective and pathologic responses were uncommon; which may be related to a short course of therapy. Our study included a higher percentage of patients with node positive disease, and older patients not included in previous FOLFIRINOX studies (27% age ≥ 70 years). There is a need for a larger study and a longer follow up to detect a signal of efficacy.

Citation Format: Safi Shahda, Michael G. House, C Max Schmidt, Attila Nakeeb, Amikar Sehdev, Jingmei Lin, Harvey M. Cramer, Yan Tong, Janet R. Flynn, Nicholas J. Zyromski, Bert H. O’Neil.{Authors}. Neoadjuvant FOLFIRINOX in patients with resectable pancreatic cancer. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2016 May 12-15; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(24 Suppl):Abstract nr B89.