Abstract
The combination of fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) is the standard of care for advanced pancreatic cancer, but causes hematological and gastrointestinal toxicities, leading to treatment delay and dose reduction; optimal modification based on toxicities is needed. Therefore, we evaluated the effect of initial relative dose intensity (RDI) on FOLFIRINOX efficacy by conducting a Japanese nationwide survey. We evaluated overall survival (OS) and progression-free survival (PFS) of patients administered two or more cycles of FOLFIRINOX, and determined RDIs for each drug within the first two cycles. RDI’s effect on efficacy was evaluated using a multivariate analysis with a Cox regression hazard model. Of 399 patients enrolled, 359 and 346 were evaluated for OS and PFS, respectively. Median RDI was 71.8%, 64.7%, 23.4%, and 76.9% for oxaliplatin, irinotecan, and bolus and continuous infusions of 5-FU, respectively. A high RDI for 5-FU bolus resulted in poor prognosis in terms of PFS (hazard ratio: 1.34; p = 0.022) and negatively correlated with objective response (coefficient: −0.70; p = 0.021), and a high RDI for CPT-11 positively correlated with objective response (coefficient: 1.02; p = 0.031). In conclusion, low and high RDIs for irinotecan and 5-FU bolus, respectively, resulted in poor FOLFIRINOX efficacy.
Highlights
Pancreatic adenocarcinoma is the fourth leading cause of death in the US and accounted for approximately 40,000 deaths in 2014 [1]
We compared the efficacy of FOLFIRINOX in patients with advanced pancreatic cancer who received drugs at high and low relative dose intensity (RDI) in the first two cycles to evaluate the impact of RDI on treatment efficacy
The initial RDIs for 5-FU bolus had a negative correlation with progressionfree survival (PFS) and objective response, whereas the RDIs for CPT-11 had a positive effect on objective response
Summary
Pancreatic adenocarcinoma is the fourth leading cause of death in the US and accounted for approximately 40,000 deaths in 2014 [1]. It was the fourth leading cause of death in Japan in 2013 [2]. Various systemic chemotherapies have been evaluated for the management of advanced pancreatic adenocarcinoma. The combination of 5-fluorouracil (5-FU), leucovorin (l-LV), irinotecan (CPT-11), and oxaliplatin (L-OHP), FOLFIRINOX, has been shown to improve overall survival (OS) in patients with metastatic pancreatic adenocarcinoma compared with gemcitabine treatment [3]. FOLFIRINOX is the standard of care in the treatment guideline for metastatic pancreatic adenocarcinoma [4]
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