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Intra-arterial gemcitabine versus intravenous gemcitabine: Pharmacokinetic and pharmacodynamic sub-study of the TIGeR-PaC phase 3 clinical trial
Abstract   Open access   Peer reviewed

Intra-arterial gemcitabine versus intravenous gemcitabine: Pharmacokinetic and pharmacodynamic sub-study of the TIGeR-PaC phase 3 clinical trial

Paula M. Novelli, Amer H. Zureikat, Michael J. Pishvaian, Kenneth Meredith, Hassan Hatoum, Emmanuel E. Zervos, Reza Nazemzadeh, Sandeep Laroia, Pashtoon Murtaza Kasi and Ramtin Agah
Journal of clinical oncology, Vol.44(2_suppl), pp.732-732
01/10/2026
DOI: 10.1200/JCO.2026.44.2_suppl.732
url
https://doi.org/10.1200/JCO.2026.44.2_suppl.732View
Published (Version of record) Open Access

Abstract

732 Background: Localized, dual balloon catheter-mediated, intra-arterial delivery of gemcitabine (IAG) targeted to tumors/tissue can provide higher local drug potency. 1 Furthermore, IAG may result in decreased systemic drug concentration and associated side effects with superior tumor response due to intra-cellular delivery prior to conversion to its inactive metabolite, diflourodeoxyuridine (dF/dU). The ongoing TIGeR-PaC phase 3 trial is testing this approach in patients with locally advanced pancreatic cancer. Here we report the results of an 11-patient pharmacokinetics (PK) sub-study analysis within TIGeR-PaC. An association between systemic drug levels and a reduction in CA19-9 markers was also assessed. Methods: PK analyses were performed for a total of 16 participants across 6 TIGeR-PaC study sites; 11 participants received IAG with the RenovoCath dual balloon catheter at 1000 mg/m 2 over 20 minutes and 5 received intravenous gemcitabine (IVG) at 1000 mg/m 2 over 30 minutes. Blood was collected at T = -5, 10, 15, 20, 30, 40, 60, and 90 minutes from the onset of infusion. Plasma from each sample was frozen and shipped to a reference lab for gemcitabine and dF/dU assays. Maximum plasma drug concentration (C max ) and the area under the drug plasma concentration curve (AUC) based on the terminal phase were compared between the two groups. CA19-9 levels were also measured prior to treatment and 2 weeks post-procedure. Results: As previously shown, IAG results in lower gemcitabine C max and AUC compared to IVG. 2 Additional analyses showed the dF/dU C max and AUC were higher for IAG compared to IVG, consistent with a more rapid conversion of gemcitabine to dF/dU with targeted IAG compared to systemic IVG. With IAG administration, there was a direct correlation between increased dF/dU levels and reduced CA19-9 levels ( r = 0.66). These results suggest the conversion of gemcitabine to dF/dU at the tissue level may provide a surrogate marker for drug response with IAG administration. Conclusions: In this analysis, localized, dual-balloon catheter-mediated IAG resulted in decreased systemic levels of gemcitabine compared to IVG, along with increased levels of its inactive metabolite dF/dU. Thus, in addition to providing increased local potency, the IAG approach, in which gemcitabine is rapidly converted to its inactive metabolite, may also be beneficial in decreasing gemcitabine-related systemic side effects. 1. Farsad K, et al. 2024. JVIR 35:1043-48 e3. 2. Novelli P, et al. 2025. J Clin Oncol 43(4_suppl):719. Clinical trial information: NCT03257033 . Effects of treatment mode on mean pharmacokinetic parameters. PK parameter, mean (SD) IAG Group(N=11) IVG Group(N=5) Gemcitabine: C max (mcg/mL) 12.9 (8.03) 14.6 (2.66) AUC (hr ⋅ mcg/mL) 4.9 (3.10) 8.8 (2.22) dF/dU: C max (mcg/mL) 48.3 (18.6) 30.6 (4.93) AUC (hr ⋅ mcg/mL) 46.3 (15.2) 37.1 (5.21)
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