Treatment of locally advanced pancreatic cancer using localized trans-arterial micro perfusion of gemcitabine: combined analysis of RR1 and RR2.

BACKGROUND: Locally advanced pancreatic cancer (LAPC) comprises 40% of pancreatic cancer diagnoses and has a relatively poor prognosis. Trans-arterial micro perfusion (TAMP)-mediated chemotherapy delivery to the primary tumor is a novel approach worthy of investigation. The RR1 (dose escalation) and RR2 (observational) studies examined the safety and preliminary efficacy of TAMP-delivered gemcitabine for LAPC. PATIENTS AND METHODS: RR1 and RR2 data were pooled. Both studies enrolled patients with LAPC with histologically confirmed adenocarcinoma. Participant data, including age, sex, race, stage, previous treatments, toxicity, disease progression, and death, were collected. Median number of cycles and average treatment dosage were calculated. Overall survival (OS) was determined for the whole group and separately for patients who received and did not receive previous treatments. Aims of the analysis were to assess procedure safety, OS, and evaluate factors associated with OS. RESULTS: The median age of the 43 patients enrolled in RR1 and RR2 was 72 years (range, 51-88 years). Median OS for the 35 eligible patients with stage III disease was 12.6 months (95% CI, 2.1-54.2 months). Previous chemoradiation was associated with significantly longer OS [27.1 months (95% CI, 8.4-40.6 months)] compared to previous systemic chemotherapy [14.6 months (95% CI, 6.4-54.2 months)] or no prior treatment [7.0 months (95% CI, 2.1-35.4 months)] (P < .001). The most common adverse events were GI related (abdominal pain, emesis, and vomiting); the most common grade 3 toxicity was sepsis. CONCLUSION: Study results indicate that TAMP-mediated gemcitabine delivery in patients with LAPC is potentially safe, feasible, and provides potential clinical benefits. CLINICAL TRIAL REGISTRATION: NCT02237157 (RR1) and NCT02591082 (RR2).

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

Purpose: This is a first-in-man safety study in locally advanced pancreatic cancer (LAPC) using a targeted intra-arterial delivery catheter (RenovoCath™). Methods: Twenty patients were enrolled in a four-stage dose escalation of intra-arterial, locally delivered gemcitabine, at doses up to 1000 mg/m2. Patients' symptoms and laboratory values were monitored for safety and tolerability. Secondary endpoints included the effect on tumor size, tumor markers, and survival. Results: 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 (n = 3), grade 3 neutropenia (n = 3), guide-mediated vascular dissection (n = 3), and pulmonary toxicity (n = 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%. Conclusions: 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.