Abstract 1544P
Background
Neoadjuvant therapy is an increasingly used approach in patients with resectable pancreatic cancer (PC). A positive link between chemotherapy dose intensity and patients’ outcome has been suggested in other PC settings. The aim of this study was to assess whether 5-FU pharmacokinetic (PK) parameters correlate with outcome in resected PC patients treated with preoperative FOLFOXIRI.
Methods
From January 2012 to November 2019 patients with potentially resectable PC treated with mFOLFOXIRI regimen (5-FU initial dose of 3200 mg/m2 in 46h infusion and subsequent doses based on PK-guided dose adjustments targeting an AUC of 25-30 mcg*h/ml) were included. 5-FU PK analysis was performed taking two plasma samples during 5-FU infusion in at least two cycles. Drug concentrations were analysed by High-Perfomance Liquid Chromatography. After induction polychemotherapy (IPCT), patients with no progressive disease received chemo radiation (50.4 Gy with concurrent Capecitabine) followed by surgical resection. An exploratory analysis with ROC curves was performed to assess progression free survival (PFS) based on 5-FU AUC values.
Results
Forty-one patients were retrospectively assessed, 33 (80.5%) completed multimodal neoadjuvant approach and 8 (19.5%) underwent surgery after IPCT. Mean age was 63.66 (40-76). In the intention-to-treat analysis, R0 resection rate was 90%; pathological response according to CAP classification was 0, 1, 2 and 3 in 7.3, 22, 51.2 and 19.5%, respectively; and lymph node infiltration (ypN1), vascular and perineural invasion was described in 22, 7.3 and 39% of patients, respectively. Mean 5-FU AUC was 29 mcg*h/ml (21-53.4). Mean PFS and OS for patients with a 5-FU AUC ≥27 mcg*h/ml was 35 and 40 months, compared to 18 and 22 months in patients with a 5-FU AUC < 27 mcg*h/ml (HR for disease progression 0.321; 95% CI = 0.110-0.940; p = 0.038, HR for death 0.405; 95% CI = 0.184 – 0.997; p = 0.049), in a model controlled by age, sex, resectability and irinotecan dose intensity. There were no differences in G3-4 IPCT-related toxicities according to 5-FU AUC cut-off.
Conclusions
5-FU dose optimization to reach an AUC target of ≥ 27 mcg*h/ml by means of pharmacokinetic parameters seems to correlate with longer PFS and OS in this setting.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.