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

Authors

Janet E. Murphy, MD, MPH;  Jennifer Y.Wo, MD; David P. Ryan, MD;  Wenqing Jiang, MS;  Beow Y. Yeap, ScD;  Lorraine C. Drapek, NP, PhD;  Lawrence S. Blaszkowsky, MD;  Eunice L. Kwak, MD, PhD;  Jill N. Allen, MD;  JeffreyW. Clark, MD;  Jason E. Faris, MD;  Andrew X. Zhu, MD, PhD;  Lipika Goyal, MD, MPhil;  Keith D. Lillemoe, MD;  Thomas F. DeLaney, MD;  Carlos Fern.ndez-del Castillo, MD;  Cristina R. Ferrone, MD;  Theodore S. Hong, MD

Purpose

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.

Methods

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

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

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.