Abstract

Background: The combination of 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) is a very effective chemotherapeutic regimen for unresectable pancreatic cancer. Previous studies have reported that female gender may be a predictor of a better response to FOLFIRINOX. This study was aimed at investigating the clinical outcomes and dose modification patterns of FOLFIRINOX by gender. Methods: Patients with metastatic pancreatic cancer (MPC) who began FOLFIRINOX as the first-line therapy at Seoul National University Bundang Hospital between 2013 and 2018 were enrolled. The patients received at least four chemotherapy cycles. Local regression and a linear mixed model were used to analyze dose modification patterns by gender. Results: Ninety-seven patients with MPC (54 men; 43 women) were enrolled. In the first FOLFIRINOX cycle, there were significant differences in age and body surface area between the genders (58.8 (men) and 64.9 years (women), p = 0.005; 1.7 (men) and 1.6 m2 (women), p < 0.001, respectively). The median progression-free survival (PFS) and overall survival (OS) were 10.8 and 18.0 months, respectively. There was a trend of longer PFS (10.3 (men) and 11.9 months (women), p = 0.153) and a significantly longer OS (17.9 (men) and 25.9 months (women), p = 0.019) in female patients. During the first year of FOLFIRINOX treatment, there was a significant difference of the age-corrected dose reduction pattern by gender (a mean of 95.6% dose at the initial cycle and −0.35% of dose reduction per week in men versus a mean of 90.7% dose at the initial cycle and −0.53% of dose reduction per week in women, p-value of the slope: <0.001). There was no difference in the adverse event rates between the genders. Conclusions: Female patients showed longer OS despite a more rapid dose reduction during each cycle. Gender differences should be considered during FOLFIRINOX treatment.

Highlights

  • IntroductionIn up to 85% of patients, pancreatic cancer is diagnosed at an advanced stage because of infiltration of the surrounding vessels or distant metastasis [2]

  • Pancreatic cancer is a lethal malignancy and the fourth leading cause of cancer-related death in the United States, with a current 5-year survival rate of only approximately 9% [1].In up to 85% of patients, pancreatic cancer is diagnosed at an advanced stage because of infiltration of the surrounding vessels or distant metastasis [2]

  • In patients with metastatic pancreatic cancer (MPC), the combination of 5-fluorouracil (5-FU), leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) or gemcitabine and nab-paclitaxel resulted in significantly longer overall survival (OS) than that associated with gemcitabine monotherapy [3,4]

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Summary

Introduction

In up to 85% of patients, pancreatic cancer is diagnosed at an advanced stage because of infiltration of the surrounding vessels or distant metastasis [2]. In patients with metastatic pancreatic cancer (MPC), the combination of 5-fluorouracil (5-FU), leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) or gemcitabine and nab-paclitaxel resulted in significantly longer overall survival (OS) than that associated with gemcitabine monotherapy [3,4]. The mechanism of FOLFIRINOX is regarded as synergistic activity of irinotecan when it is administered before fluorouracil and leucovorin and synergistic activity of irinotecan and oxaliplatin [3]. The regimen has been associated with a high incidence of adverse events, including grade 3 or 4 neutropenia and fatigue

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