Predictive factors of FOLFIRINOX chemotherapy toxicity in pancreatic adenocarcinoma patients

Future Oncol. 2025 Mar;21(6):691-697. doi: 10.1080/14796694.2025.2461442. Epub 2025 Feb 9.

Abstract

Introduction: FOLFIRINOX, a primary chemotherapy for metastatic pancreatic cancer, often causes severe toxicity, necessitating hospitalization and dose adjustments. This study aims to identify predictors of FOLFIRINOX toxicity, focusing on biological, clinical, and anthropometric factors.

Material & methods: This retrospective study analyzes pancreatic adenocarcinoma patients on FOLFIRINOX, assessing pre-treatment biological, clinical, and anthropometric traits. Hospitalizations and tolerance during the first chemotherapy month were evaluated using CTCAE v5.0 grading, with early toxicity assessed via anthropometric factors using Anthropometer3DNet software from pre-treatment scans.

Results: In 152 pancreatic cancer patients (median age: 62), FOLFIRINOX was administered in metastatic (81%), locally advanced (14%), and adjuvant/neoadjuvant (5%) settings. Performance Status was zero (49%), one (41%) and ≥ 2 (10%). Median follow-up was 62.5 months, with median overall survival of 13.7 months and progression-free survival of 8.9 months. First-cycle dose reduction occurred in 14% of patients. Within the first month, 48% experienced toxicity leading to hospitalization and/or dose reduction, with 28% requiring a median 8-day hospitalization. Low muscle body mass (MBM) significantly correlated with dose reduction (AUC 0.63; p = 0.005). An NLR ratio less than 4 was significantly associated with longer OS (p = 0.001).

Conclusion: Low MBM is linked to FOLFIRINOX toxicity, suggesting MBM assessment could allow better selection of patients to avoid these toxicities, warranting further confirmation in larger cohorts.

Keywords: FOLFIRINOX; Pancreatic adenocarcinoma; anthropometric; survival; toxicity.

MeSH terms

  • Adenocarcinoma* / drug therapy
  • Adenocarcinoma* / mortality
  • Adenocarcinoma* / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols* / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols* / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / adverse effects
  • Fluorouracil / therapeutic use
  • Humans
  • Irinotecan / administration & dosage
  • Irinotecan / adverse effects
  • Irinotecan / therapeutic use
  • Leucovorin / administration & dosage
  • Leucovorin / adverse effects
  • Leucovorin / therapeutic use
  • Male
  • Middle Aged
  • Oxaliplatin / administration & dosage
  • Oxaliplatin / adverse effects
  • Pancreatic Neoplasms* / drug therapy
  • Pancreatic Neoplasms* / mortality
  • Pancreatic Neoplasms* / pathology
  • Prognosis
  • Retrospective Studies

Substances

  • Leucovorin
  • Oxaliplatin
  • Fluorouracil
  • folfirinox
  • Irinotecan