Relationship between initial dose, dose intensity, and survival in unresectable pancreatic cancer treated with nanoliposomal irinotecan, fluorouracil, and folinic acid

Abstract

While nanoliposomal irinotecan with fluorouracil and folinic acid (NFF) is a standard second-line regimen for unresectable pancreatic cancer (uPC) after gemcitabine-based therapy, the effects of initial dosing and relative dose intensity (RDI) in routine practice are unclear. We retrospectively analyzed 161 patients (median age 67 years; 55% male) with uPC treated with NFF at 20 Japanese institutions (June 2020–May 2021), comparing standard vs. reduced starting dose and RDI ≥80% vs. <80%. Overall survival (OS) was 8.1 vs. 8.8 months for standard vs. reduced dose ( p = 0.47; hazard ratio [HR], 1.15) and 7.5 vs. 9.2 months for RDI ≥80% vs. <80% ( p = 0.39; HR, 0.85). Progression-free survival (PFS) was 3.4 vs. 3.2 months ( p = 0.43) and 2.8 vs. 4.4 months ( p = 0.13), respectively, with similar response and disease control rates. Anemia, thrombocytopenia, and vomiting occurred more frequently in patients administered the standard starting dose, whereas severe non-hematologic adverse events were more frequently observed for RDI <80%. Reduced starting dose and RDI <80% were not associated with inferior survival, suggesting that individualized dose modification may be feasible. Future prospective studies are warranted to refine NFF dosing strategies.