Total Neoadjuvant Therapy With FOLFIRINOX Followed by Individualized Chemoradiotherapy for Borderline Resectable Pancreatic Adenocarcinoma: A Phase 2 Clinical Trial | Gastroenterology | JAMA Oncology | JAMA Network
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Original Investigation
July 2018

Total Neoadjuvant Therapy With FOLFIRINOX Followed by Individualized Chemoradiotherapy for Borderline Resectable Pancreatic Adenocarcinoma: A Phase 2 Clinical Trial

Author Affiliations
  • 1Division of Hematology/Oncology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston
  • 2Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston
  • 3Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston
JAMA Oncol. 2018;4(7):963-969. doi:10.1001/jamaoncol.2018.0329
Key Points

Question  What is the association of total neoadjuvant treatment with chemotherapy and radiotherapy with margin-negative (R0) resection rates in borderline-resectable pancreatic ductal adenocarcinoma?

Findings  In this single-arm phase 2 clinical trial of 48 patients, 32 underwent surgery after total neoadjuvant therapy. In this group, 31 patients (97%) achieved R0 resection, a significantly higher rate than historical controls, which translated into a 65% R0 resection rate among all evaluable patients.

Meaning  Total neoadjuvant therapy with FOLFIRINOX (fluorouracil, irinotecan, and oxaliplatin) achieves a high rate of R0 resection in patients with borderline-resectable pancreatic ductal adenocarcinoma, a result that correlates with prolonged median progression-free and overall survival.


Importance  Patients with borderline-resectable pancreatic ductal adenocarcinoma have historically poor outcomes with surgery followed by adjuvant chemotherapy. Evaluation of a total neoadjuvant approach with highly active therapy is warranted.

Objective  To evaluate the margin-negative (R0) resection rate in borderline-resectable pancreatic ductal adenocarcinoma after neoadjuvant FOLFIRINOX (fluorouracil, irinotecan, and oxaliplatin) therapy and individualized chemoradiotherapy.

Design, Setting, and Participants  A single-arm, phase 2 clinical trial was conducted at a large academic hospital with expertise in pancreatic surgery from August 3, 2012, through August 31, 2016, among 48 patients with newly diagnosed, previously untreated, localized pancreatic cancer determined to be borderline resectable by multidisciplinary review, who had Eastern Cooperative Oncology Group performance status 0 or 1 and adequate hematologic, renal, and hepatic function. Median follow-up for the analysis was 18.0 months among the 30 patients still alive at study completion.

Interventions  Patients received FOLFIRINOX for 8 cycles. Upon restaging, patients with resolution of vascular involvement received short-course chemoradiotherapy (5 Gy × 5 with protons) with capecitabine. Patients with persistent vascular involvement received long-course chemoradiotherapy with fluorouracil or capecitabine.

Main Outcomes and Measures  The primary outcome was R0 resection rate; secondary outcomes were median progression-free survival (PFS) and median overall survival (OS).

Results  Of the 48 eligible patients, 27 were men and 21 were women, with a median age of 62 years (range, 46-74 years). Of the 43 patients who planned to receive 8 preoperative cycles of chemotherapy, 34 (79%) were able to complete all cycles. Twenty-seven patients (56%) had short-course chemoradiotherapy, while 17 patients (35%) had long-course chemoradiotherapy. R0 resection was achieved in 31 of the 48 eligible patients (65%; 95% CI, 49%-78%). Among the 32 patients who underwent resection, the R0 resection rate was 97% (n = 31). Median PFS among all eligible patients was 14.7 months (95% CI, 10.5 to not reached), with 2-year PFS of 43%; median OS was 37.7 months (95% CI, 19.4 to not reached), with 2-year OS of 56%. Among patients who underwent resection, median PFS was 48.6 months (95% CI, 14.4 to not reached) and median OS has not been reached, with a 2-year PFS of 55% and a 2-year OS of 72%.

Conclusions and Relevance  Preoperative FOLFIRINOX followed by individualized chemoradiotherapy in borderline resectable pancreatic cancer results in high rates of R0 resection and prolonged median PFS and median OS, supporting ongoing phase 3 trials.

Trial Registration Identifier: NCT01591733