Safety Study of Targeted and Localized Intra-Arterial Delivery of Gemcitabine in Patients with Locally Advanced Pancreatic Adenocarcinoma.

This is a first-in-man safety study in locally advanced pancreatic cancer (LAPC) using a targeted intra-arterial delivery catheter (RenovoCath™). Twenty patients were enrolled in a four-stage dose escalation of intra-arterial, locally delivered gemcitabine, at doses up to 1000 mg/m. Patients' symptoms and laboratory values were monitored for safety and tolerability. Secondary endpoints included the effect on tumor size, tumor markers, and survival. One hundred one treatments were administered to 20 patients. Five patients dropped out early due to adverse events or withdrawing consent. Serious adverse events and complications were as follows: sepsis ( = 3), grade 3 neutropenia ( = 3), guide-mediated vascular dissection ( = 3), and pulmonary toxicity ( = 1). There were no cases of elevated liver or pancreatic enzymes. All sepsis cases occurred in patients with biliary stent/drains, prompting the addition of periprocedural treatment with antibiotics, which effectively prevented further sepsis in the study. Efficacy analysis was limited to 15 patients who received more than two treatments. Fifty-eight percent of these patients had a reduction in CA 19-9 tumor markers, 3 patients had tumor progression, 1 had partial response, and 11 showed disease stability. The survival rate at 12 months was 60%. The results demonstrate feasibility of localized and selective intra-arterial chemotherapy delivery to the pancreas utilizing the RenovoCath. With gemcitabine, this approach is safe, with the sole prerequisite of perioperative antibiotics for patients with prior biliary drainage/stent. Efficacy results suggest a survival benefit when compared to historical control, especially in patients with prior radiation therapy.