FOLFIRINOX for locally advanced pancreatic cancer: Results and prognostic factors of subset analysis from a nation-wide multicenter observational study in Japan

Abstract

Background

FOLFIRINOX (oxaliplatin, irinotecan, 5-fluorouracil, leucovorin) treatment significantly improved overall survival in the recent phase III study and became a standard therapy for metastatic pancreatic cancer. However, treatment for locally advanced pancreatic cancer is still controversial. We conducted subset analyses from a nation-wide multicenter observational study in Japan to evaluate the tolerability and efficacy of FOLFIRINOX in patients with locally advanced pancreatic cancer and to investigate independent prognostic factors with pre-treatment variables.

Methods

The study included 66 patients with unresectable locally advanced pancreatic cancer from 27 institutions in Japan who received FOLFIRINOX as first-line treatment between December 20, 2013 and December 19, 2014 and surveyed until December 2015.

Results

The median age was 63 with the Eastern Cooperative Oncology Group performance status of 0 or 1. Major Grade 3 or 4 adverse events included neutropenia (64%), leukopenia (33%), febrile neutropenia (15%), and diarrhea (15%). Severe adverse event occurred in 14 patients (11%) without fatal event. The median overall survival and progression-free survival times were 18.5 and 7.6 months, respectively. The objective response rate 15.2% and the disease control rate was 81.9%. A high modified Glasgow prognostic score (mGPS, ≥1) (95%CI 1.96–12.5) and female (95%CI 0.20–0.97) were identified as independent poor prognostic factors.

Conclusions

First-line FOLFIRINOX treatment for locally advanced pancreatic cancer seems to be effective with acceptable toxicities. A high mGPS may be associated with poor survival in patients with locally advanced pancreatic cancer who receive FOLFIRINOX. This study was registered at the UMIN Clinical Trials Registry (UMIN000014658).

Introduction

Pancreatic cancer remains one of the most lethal malignancies, with a 5-year survival rate of less than 10% in all patients. And pancreatic cancer is the fourth leading cause of cancer death in Japan and its incidence has been increasing. At the time of diagnosis, about 30% of patients have locally advanced pancreatic cancer, which is considered surgically unresectable due to local involvement of adjacent vessels.

In the recent phase III study conducted by Conroy et al. (PRODIGE4/ACCORD11), FOLFIRINOX (oxaliplatin, irinotecan, fluorouracil [5-FU], leucovorin) significantly improved overall survival (OS), progression-free survival (PFS), and quality of life compared with gemcitabine alone in patients with metastatic pancreatic cancer [1]. The median OS and PFS times were 11.1 and 6.4 months in the FOLFIRINOX group compared to 6.8 and 3.3 months in the gemcitabine group, respectively. Currently, FOLFIRINOX has become one of the standard treatments for patients with metastatic pancreatic cancer. Although systemic chemotherapy is the main treatment for patients with both locally advanced and metastatic pancreatic cancer, no randomized controlled study has been conducted of FOLFIRINOX in patients with locally advanced pancreatic cancer. A recent phase II study and many observational studies indicate that FOLFIRINOX has a survival benefit in locally advanced pancreatic cancer when compared with historical controls [[2], [3], [4], [5], [6], [7]]. However, the sample sizes of most studies have been too small to draw definitive conclusions as to the efficacy and safety of FOLFIRINOX for patients with locally advanced pancreatic cancer. In particular, there has been no report of FOLFIRINOX in Japanese patients with locally advanced pancreatic cancer.

The optimal treatment regimen for locally advanced pancreatic cancer is still controversial and current guidelines are not consistent including various regimens of chemotherapy, chemoradiotherapy, and induction chemotherapy. Although many treatment options are provided for locally advanced pancreatic cancer, evidence and guidance are limited as to the best treatment for individual cases. Our group previously reported the results of a nationwide multicenter observational study of FOLFIRINOX chemotherapy in 399 patients with unresectable or recurrent pancreatic cancer in Japan [8]. The median overall survival times and progression-free survival times were 10.8, and 4.5 months, respectively. The study concluded that FOLFIRINOX was efficient with acceptable safety in Japanese patients.

In this study, we conducted subgroup analyses to evaluate the tolerability and efficacy of FOLFIRINOX in patients with locally advanced pancreatic cancer as first-line treatment and to investigate independent prognostic factors with pretreatment variables in Japanese patients.