Adjuvant Chemotherapy for Pancreatic Ductal Adenocarcinoma with GEMCAP and mFOLFIRINOX Regimens: Adverse Events and Long-Term Outcomes

Abstract

Introduction. Adjuvant chemotherapy remains the standard of care for pancreatic adenocarcinoma following radical surgery. It is necessary to evaluate the efficacy and toxicity of the most common adjuvant chemotherapy regimens to achieve optimal treatment outcomes.

Aim. To compare the toxicity profiles of adjuvant chemotherapy regimens GEMCAP and mFOLFIRINOX for pancreatic ductal adenocarcinoma and assess their impact on long-term outcomes.

Materials and Methods. Retrospective analysis of 128 patients (GEMCAP: n=60; mFOLFIRINOX: n=68) after radical surgery. Adverse events, dose intensity, 3-year relapse-free survival (RFS), and overall survival (OS) were evaluated.

Results. The GEMCAP regimen was associated with a higher incidence of grade III–IV neutropenia (45% vs. 27.9%, p=0.06), while mFOLFIRINOX was associated with more grade II–III diarrhea (20.6% vs. 0%, p<0.01) and elevated ALT/AST levels (20.6% vs. 3.3%, p=0.006). Three-year RFS was superior for the mFOLFIRINOX group (36% vs. 19%, p=0.03). OS showed a trend favoring mFOLFIRINOX (68% vs. 52%, p=0.07). Gemcitabine dose reduction in the GEMCAP regimen significantly worsened RFS (3-year RFS: 27% without dose reduction vs. 6% with dose reduction, p=0.02), whereas irinotecan dose reduction in the mFOLFIRINOX regimen did not affect outcomes (p>0.05). RFS for patients with a hemoglobin, albumin, lymphocyte, and platelet (HALP) score ≥48.8 was significantly longer (median 29.8 months) compared to those with a HALP score <48.8 (median 15.7 months, p=0.024).

Conclusion. mFOLFIRINOX offers superior survival but higher hepatotoxicity and diarrhea. Reducing the irinotecan dose (to 130 mg/m²) in mFOLFIRINOX may improve tolerability without compromising efficacy. Maintaining dose intensity is critical for achieving optimal RFS in GEMCAP. Furthermore, patients with a low HALP score had significantly shorter RFS.