A retrospective study of neoadjuvant FOLFIRINOX in unresectable or borderline-resectable locally advanced pancreatic adenocarcinoma

Arturo Loaiza-Bonilla,Jessica Macintyre,Joe U Levi,Peter J Hosein,Caio M Rocha-Lima,Afonso Ribeiro,Carolina Kawamura,Lorraine Portelance,Govindarajan Narayanan,Jaime R Merchan,Jennifer Cudris Maldonado,Vinicius Ernani

doi:10.1186/1471-2407-12-199

Abstract

Background5-fluorouracil, leucovorin, irinotecan and oxaliplatin (FOLFIRINOX) is superior to gemcitabine in patients with metastatic pancreatic cancer who have a good performance status. We investigated this combination as neoadjuvant therapy for locally advanced pancreatic cancer (LAPC).MethodsIn this retrospective series, we included patients with unresectable LAPC who received neoadjuvant FOLFIRINOX with growth factor support. The primary analysis endpoint was R0 resection rate.ResultsEighteen treatment-naïve patients with unresectable or borderline resectable LAPC were treated with neoadjuvant FOLFIRINOX. The median age was 57.5 years and all had ECOG PS of 0 or 1. Eleven (61 %) had tumors in the head of the pancreas and 9 (50 %) had biliary stents placed prior to chemotherapy. A total of 146 cycles were administered with a median of 8 cycles (range 3-17) per patient. At maximum response or tolerability, 7 (39 %) were converted to resectability by radiological criteria; 5 had R0 resections, 1 had an R1 resection, and 1 had unresectable disease. Among the 11 patients who remained unresectable after FOLFIRINOX, 3 went on to have R0 resections after combined chemoradiotherapy, giving an overall R0 resection rate of 44 % (95 % CI 22–69 %). After a median follow-up of 13.4 months, the 1-year progression-free survival was 83 % (95 % CI 59-96 %) and the 1-year overall survival was 100 % (95 % CI 85-100 %). Grade 3/4 chemotherapy-related toxicities were neutropenia (22 %), neutropenic fever (17 %), thrombocytopenia (11 %), fatigue (11 %), and diarrhea (11 %). Common grade 1/2 toxicities were neutropenia (33 %), anemia (72 %), thrombocytopenia (44 %), fatigue (78 %), nausea (50 %), diarrhea (33 %) and neuropathy (33 %).ConclusionsFOLFIRINOX followed by chemoradiotherapy is feasible as neoadjuvant therapy in patients with unresectable LAPC. The R0 resection rate of 44 % in this population is promising. Further studies are warranted.

Highlights

Pancreatic cancer carries a dismal prognosis with a 5year overall survival rate of 6 %
Patients were selected for treatment with FOLFIRINOX if they had a histological or cytological diagnosis of pancreatic adenocarcinoma, an Eastern Cooperative Group performance status (ECOG PS) of 0 or 1, adequate organ function, and UR/borderline resectable (BR) locally advanced pancreatic cancer (LAPC)
One patient was defined as unresectable at the time of exploratory laparotomy and the remaining patients fulfilled criteria for UR/BR disease based on CECT and endoscopic ultrasound (EUS) findings

Summary

Introduction

Pancreatic cancer carries a dismal prognosis with a 5year overall survival rate of 6 %. It is the fourth leading cause of cancer death in the USA with an estimated 37,660 deaths in 2011 [1]. The RR in the FOLFIRINOX arm was 32 % versus 9 % in the gemcitabine arm, and this translated into an improvement in PFS to 6.4 months (versus 3.3 in the control arm, p < 0.0001) and OS of 11.1 months (versus 6.8 months in the control arm, p < 0.0001) This trial only enrolled patients with metastatic pancreatic cancer. In the setting of LAPC, a good tumor response is a desirable goal since tumor shrinkage away from vascular structures may lead to resectability

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