Intra-arterial gemcitabine vs IV gemcitabine PK substudy in patients with locally advanced pancreatic cancer.

Abstract

728 Background: Localized dual-balloon-mediated, intra-arterial delivery of Gemcitabine (IAG) directly into tumors/tissue can lead to higher local drug potency1. Furthermore, IAG may lead to decreased systemic drug concentration and associated side effects. In patients with Locally Advanced Pancreatic Cancer (LAPC), this approach is currently being tested in a contemporary Phase III clinical trial, TIGeR-PaC. Herein we report the results of a 10-patient PK analysis sub-study within TIGeR-PaC. Methods: We analyzed a total of 10 subjects from 5 sites who received intra-arterial gemcitabine with the RenovoCath dual balloon catheter at 1000mg/m2 over 20 minutes. The target treatment artery was either the celiac axis (n=5) or the superior mesenteric artery (n=5). Samples were drawn at T = -5, 10, 15, 20, 30, 40, 60, and 90 minutes from the onset of infusion. At each timepoint, we collected 2mL of blood in heparinized tubing containing 25 mcg/mL of tetrahydrouridine. The blood samples were then centrifuged collect, freeze, and ship the plasma to a reference lab to perform a gemcitabine assay. The PK parameters for a single dose was estimated for Cmax, AUC, clearance, and distribution volume based on the terminal phase. These values are compared to historical data for intravenous gemcitabine (IVG) infusion at 1000mg/m2 over 30 minutes2. Results: At this time, data has been analyzed for 4 of 8 collected samples. We expect to complete collection and analysis of all 10 samples by November of 2022. We show results available so far; historical values for IVG are given as a reference point. The results suggest that IAG is associated with decreased systemic exposure of gemcitabine compared to IVG. Conclusions: Localized dual-balloon-mediated, intra-arterial delivery of gemcitabine can lead to decreased systemic levels of gemcitabine. This approach increased local potency and may be beneficial in decreasing gemcitabine-related systemic side effects. 1. Farsad K, et al. 04:21 PM Abstract No. 392 . J Vasc Intervent Radiol 2019;30(3):S172. doi:10.1016/j.jvir.2018.12.467. 2. Chow ECY, Zirkelbach JF. Clinical Pharmacology and Biopharmaceutics Review(s) {209604Orig1s000}. FDA: Center for Drug Evaluation and Research. Clinical trial information: NCT03257033 . [Table: see text]