Analyse der dosisabhängigen Wirkung von FOLFIRINOX und der Faktoren für Dosisreduktion bei der Behandlung des Pankreaskarzinoms

Pancreatic ductal adenocarcinoma (PDAC) is among the most aggressive malignancies and is associated with a very poor prognosis. FOLFIRINOX—a combination of 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin—is currently considered the most effective systemic regimen but is accompanied by substantial toxicity. In routine practice, doses are therefore frequently reduced, particularly in patients with comorbidities and impaired performance status. However, the degree of dose reduction that preserves efficacy remains uncertain. This study evaluated the association between FOLFIRINOX dose intensity and early radiographic outcomes as well as overall survival, and examined factors associated with an initial dose reduction in cycle 1. We retrospectively analyzed a mixed PDAC cohort treated with FOLFIRINOX at the University Medical Center Göttingen. Cumulative multi-drug relative dose intensity (cmRDI) was calculated up to the first follow-up imaging to capture dose modifications and interval changes. Associations between cmRDI and radiographic response at first follow-up CT staging, as well as overall survival, were assessed using the Mann–Whitney U test, receiver operating characteristic (ROC) analysis, Kaplan–Meier estimates with log-rank testing, and Cox regression. Demographic and clinical predictors of an initial dose reduction were examined using binomial logistic regression. Among 199 patients, the median number of cycles was six and the median cmRDI was 78.7%. At first follow-up CT staging, the response rate was 43.2% and the disease control rate was 67.8%. Median overall survival was 15 months. Patients achieving disease control at first follow-up CT had a significantly higher cmRDI. ROC analysis identified a cmRDI threshold of 76% for disease control (sensitivity 66.7%, specificity 56.3%). Higher cmRDI was associated with a reduced risk of death (hazard ratio 0.981), and patients with cmRDI >76% had significantly longer overall survival than those with cmRDI 76% may represent a pragmatic target for early disease control. These findings are limited by the retrospective, single-center design and potential confounding by indication, and warrant external validation.