| Summary: | Background: Despite a potentially curative treatment, the prognosis after upfront surgery and adjuvant
chemotherapy for patients with resectable pancreatic ductal adenocarcinoma (PDAC) is poor. Modified
FOLFIRINOX (mFOLFIRINOX) is a cornerstone in the systemic treatment of PDAC, including the neoadjuvant setting. Pharmacokinetic-guided (PKG) dosing has demonstrated beneficial effects in other
tumors, but scarce data is available in pancreatic cancer.
Methods: Forty-six patients with resected PDAC after mFOLFIRINOX neoadjuvant approach and included
in an institutional protocol for anticancer drug monitoring were retrospectively analyzed. 5-Fluorouracil
(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 area under the curve (AUC) above 28 mcg$h/mL or CPT-11 AUC values below
10 mcg$h/mL. In the multivariate analyses adjusted by age, gender, performance status and resectability
after stratification according to both pharmacokinetic parameters, the risk of progression was significantly reduced in patients with 5-FU AUC 28 mcg$h/mL [HR ¼ 0.251, 95% CI 0.096e0.656; p ¼ 0.005]
and CPT-11 AUC <10 mcg$h/mL [HR ¼ 0.189, 95% CI 0.073e0.486, p ¼ 0.001].
Conclusions: Pharmacokinetically-guided dose adjustment of standard chemotherapy treatments might
improve survival outcomes in patients with pancreatic ductal adenocarcinoma.
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