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).

Double-Balloon Catheter-Mediated Transarterial Chemotherapy Delivery in a Swine Model: A Mechanism Recruiting the Vasa Vasorum for Localized Therapies.

PURPOSE: Treatment of hypovascular tumors, such as pancreatic adenocarcinoma, is challenging owing to inefficient drug delivery. This report examines the potential mechanism of localized drug delivery via transarterial microperfusion (TAMP) using a proprietary adjustable double-balloon occlusion catheter in a porcine model. MATERIALS AND METHODS: Adult Yorkshire swine (N = 21) were used in the Institutional Animal Care & Use Committee-approved protocols. The RC-120 catheter (RenovoRx, Los Altos, California) was positioned into visceral, femoral, and pulmonary arteries with infusion of methylene blue dye, gemcitabine, or gold nanoparticles. Transmural delivery was compared under double-balloon occlusion with and without side-branch exclusion, single-balloon occlusion, and intravenous delivery. Intra-arterial pressure and vascular histologic changes were assessed. RESULTS: Infusion with double-balloon occlusion and side-branch exclusion provided increased intra-arterial pressure in the isolated segment and enhanced perivascular infusate penetration with minimal vascular injury. Infusates were predominantly found in the vasa vasorum by electron microscopy. CONCLUSIONS: TAMP enhanced transmural passage mediated by localized increase in arterial pressure via vasa vasorum.