Sex Differences in Patients with Metastatic Pancreatic Cancer Who Received FOLFIRINOX

Abstract Background:The combination of 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) is a very effectivechemotherapeutic regimen forunresectable pancreatic cancer.Previous studies have reported that female sex 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 sex.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 sex.Results:Ninety-seven patients with MPC (54 men;43 women) were enrolled. In the first FOLFIRINOX cycle,there was a significant difference in age and body surface area between the sexes (58.8 [men] and 64.9 years [women], p =0.005 and 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 longerPFS (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 sex (a mean of 94.3% dose at the initial cycle and -0.34% of dose reduction per week in menversus a mean of 89.3% dose at the initial cycle and -0.51% 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 sexes.Conclusion: Female patients showed longer OS despite a more rapid dose reduction during each cycle. Sex differences should be considered during FOLFIRINOX treatment.