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We hypothesized IAG may result in decreased systemic gemcitabine concentration and associated side effects due to intracellular delivery prior to conversion to gemcitabine\u2019s inactive metabolite, difluorodeoxyuridine (dFdU). Here we report the results of a pharmacokinetics and pharmacodynamics sub-study within the TIGeR-PaC phase 3 clinical trial (NCT03257033).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Analyses were performed for 16 participants across 6 TIGeR-PaC study sites; 11 participants received localized IAG and 5 participants received systemic intravenous gemcitabine (IVG). Gemcitabine and dFdU assays were performed on blood samples collected immediately before, during, and after infusion. CA 19\u2009\u2212\u20099 levels were measured prior to and 2 weeks after IAG treatment. Maximum plasma drug concentration (C\n                      <jats:sub>max<\/jats:sub>\n                      ) and the area under the drug plasma concentration curve (AUC\n                      <jats:sub>0\u2212t<\/jats:sub>\n                      ) were compared between treatment groups. Pearson\u2019s correlation for AUC\n                      <jats:sub>0\u2212t<\/jats:sub>\n                      and the percent change in CA 19\u2009\u2212\u20099 levels was calculated for the IAG group.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      IAG resulted in lower gemcitabine C\n                      <jats:sub>max<\/jats:sub>\n                      and AUC\n                      <jats:sub>0\u2212t<\/jats:sub>\n                      and higher dFdU C\n                      <jats:sub>max<\/jats:sub>\n                      and AUC\n                      <jats:sub>0\u2212t<\/jats:sub>\n                      compared to IVG, consistent with a more rapid conversion of gemcitabine to dFdU with IAG versus IVG. With IAG, there was a significant correlation between increased dFdU levels and a pre- to post-treatment reduction in CA 19\u2009\u2212\u20099 levels (Pearson\u2019s\n                      <jats:italic>r<\/jats:italic>\n                      = -0.75;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.034).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In addition to providing increased local potency, localized IAG, in which gemcitabine is rapidly converted to its inactive metabolite dFdU, may also be beneficial in decreasing gemcitabine-related systemic side effects.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00280-026-04939-0","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T02:20:50Z","timestamp":1786933250000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacokinetic and pharmacodynamic sub-study of trans-arterial vs. intravenous gemcitabine in the TIGeR-PaC phase 3 clinical trial"],"prefix":"10.1007","volume":"96","author":[{"given":"Paula M.","family":"Novelli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel E.","family":"Zervos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amer H.","family":"Zureikat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Pishvaian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Meredith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hassan","family":"Hatoum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reza","family":"Nazemzadeh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandeep","family":"Laroia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pashtoon","family":"Kasi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justus","family":"Bingham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramtin","family":"Agah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,17]]},"reference":[{"key":"4939_CR1","doi-asserted-by":"publisher","first-page":"e217","DOI":"10.1200\/EDBK_160827","volume":"35","author":"AL Coveler","year":"2016","unstructured":"Coveler AL, Herman JM, Simeone DM, Chiorean EG (2016) Localized Pancreatic Cancer: Multidisciplinary Management. 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R.A. is an employee of and shareholder in RenovoRx and serves on the RenovoRx Board of Directors. J.B. is a paid consultant for RenovoRx. All other authors declare no potential conflicts of interest.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.","order":2,"name":"Ethics","label":"Compliance with ethical standards","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"91"}}