Optimizing Perioperative Management of Pancreatic Ductal Adenocarcinoma: Insights Into Modified FOLFIRINOX Relative Dose Intensity and CA 19-9 Dynamics

Abstract

Background

Many patients with resectable pancreatic ductal adenocarcinoma (PDAC) treated with modified FOLFIRINOX (mFOLFIRINOX) require dose reduction due to adverse effects. This study explores the optimal threshold for mFOLFIRINOX relative dose intensity (RDI) and characterizes RDI's correlation with CA 19-9.

Methods

A single-institution retrospective analysis of 97 patients with PDAC treated with mFOLFIRINOX and pancreatectomy from 2017 to 2022. RDI was calculated by dividing the delivered dose intensity by the intended dose intensity over 6 months.

Results

Median overall RDI was 73.8% (fluorouracil 75.5%, irinotecan 74.5%, oxaliplatin 70.6%). An RDI cutoff of ≥ 70% (n = 57) was associated with significantly improved overall survival (median OS: 62.6 vs. 43.7 months, p = 0.034). Compared to patients with < 70% RDI who did not achieve CA 19-9 normalization, those with ≥ 70% RDI and normalization had significantly improved survival (HR: 0.27; 95% CI: 0.11–0.73). No significant benefit was observed with ≥ 70% RDI without CA 19-9 normalization or < 70% RDI with normalization. In the multivariable model, RDI ≥ 70% remained independently associated with improved OS (HR = 0.37, 95% CI: 0.18–0.79) but not disease-free survival (HR = 0.50, 95% CI: 0.24–1.03).

Conclusion

Receiving ≥ 70% RDI of mFOLFIRINOX and CA 19-9 normalization independently improves survival in resected PDAC. The greatest benefit is observed when both are achieved.