Optimal initial relative dose intensity of modified FOLFIRINOX in pancreatic ductal adenocarcinoma: A retrospective multi-center cohort

BACKGROUND: FOLFIRINOX is a standard first-line therapy for metastatic pancreatic ductal adenocarcinoma (PDAC), but its toxicity often necessitates dose adjustments. This study evaluated the impact of first relative dose intensity (RDI) of irinotecan and oxaliplatin on treatment outcomes and safety in PDAC patients. METHODS: This retrospective multi-center cohort study included 109 PDAC patients treated with FOLFIRINOX across 12 Taiwanese hospitals from 2017 to 2020. Initial RDI was defined as the ratio of actual to standard doses of irinotecan and oxaliplatin in the first cycle. Patients were categorized into three RDI groups: <70%, 70-90%, and ≥90%. RESULTS: The median PFS was 5.1 months and median OS was 11.6 months. In the <70%, 70-90%, and ≥90% RDI groups, median PFS was 4.9, 7.1, and 3.5 months, and median OS was 10.7, 16.2, and 7.0 months, respectively. The 70-90% group had significantly longer OS than the <70% and ≥90% groups and PFS in the 70-90% group was significantly longer than in the ≥90% group. Grade ≥3 adverse events occurred in 49.5% of patients, mainly hematologic. The ≥90% group had the highest toxicity despite receiving a median of 3.5 cycles. CONCLUSION: The initial RDI of 70-90% for irinotecan and oxaliplatin may optimize both efficacy and tolerability in Taiwanese PDAC patients treated with FOLFIRINOX.