Therapeutic drug monitoring of neoadjuvant mFOLFORINOX in resected pancreatic ductal adenocarcinoma

Background
Despite a potentially curative treatment, the prognosis after upfront surgery and adjuvant chemotherapy for patients with resectable pancreatic ductal adenocarcinoma (PC) is poor. Modified FOLFORINOX is a cornerstone in the systemic treatment of PC, including the neoadjuvant setting. Pharmacokinetic-guided dosing has demonstrated beneficial effects in other tumors, but scarce data is available in PC.

Methods
Forty-six patients with resected PC after mFOLFORINOX neoadjuvant approach and included in an institutional protocol for anticancer drug monitoring were retrospectively analyzed. 5-FU dosage was adjusted throughout neoadjuvant treatment according to pharmacokinetic parameters and Irinotecan (CPT-11) pharmacokinetic variables were retrospectively estimated.

Results
By exploratory univariate analyses, a significantly longer progression-free survival was observed for patients with either 5-FU AUC values above 28 mcg·h/mL or CPT-11 AUC values below 10 mcg·h/mL. After stratification according to both pharmacokinetic parameters, the risk of progression was significantly reduced in patients with 5-FU AUC ≥28 mcg·h/mL [HR = 0.251, 95% CI 0.096–0.656; p = 0.005] and CPT-11 AUC <10 mcg·h/mL [HR = 0.189, 95% CI 0.073–0.486, p = 0.001].

Conclusions
Pharmacokinetically-guided dose adjustment of standard chemotherapy treatments might improve survival outcomes in patients with pancreatic cancer.

CITA DEL ARTÍCULO  Pancreatology, 2023, ISSN 1424-3903,
https://doi.org/10.1016/j.pan.2023.03.001.