SURG-10. CONVECTION ENHANCED DELIVERY OF TOPOTECAN AND GADOLINIUM FOR RECURRENT GBM VIA THE CLEVELAND MULTIPORT CATHETER: A FIRST IN HUMAN STUDY

Abstract

INTRODUCTION: Convection enhanced delivery (CED) was developed as a technique to bypass barriers to effective treatment of gliomas. The Cleveland Multiport Catheter (CMC) is a novel device that was designed to produce high volume, backflow resistant CED. We have investigated the ability of the CMC to deliver a chemotherapy and tracer to enhancing and non-enhancing regions of recurrent high grade gliomas. METHODS: A Sponsor-Investigator IND covered both the CMC and drug (topotecan HCl with gadolinium DTPA). Two pilot trials were opened: the first trial evaluated delivery in both enhancing tumor and tumor-infiltrated brain, and the second trial evaluated delivery in tumor-infiltrated brain after resection of the enhancing tumor. We used MRI to evaluate the distribution of the infused gadolinium to evaluate efficacy of drug delivery. Quantitative assessment of drug distribution was made by a blinded evaluator. RESULTS: Twelve patients have been treated to date. All patients underwent successful placement of two CMCs each and completed infusions ranging from 48 to 96 hours; 3 in the first pilot trial and 9 in the second trial. Intraoperative and peri-operative MRIs demonstrated tracer delivery from every CMC placed to date (24 catheters, 96 microcatheters) without obvious backflow along the CMC shaft. We found large differences in the volumes of distribution between catheters placed in enhancing versus nonenhancing, tumor infiltrated brain, with high volumes of distribution (range: 25 to 92 cc) observed in the patients whose treatment focused on tumor infiltrated brain. There were no hemorrhages related to catheter placement or removal. Infusion related safety data will be presented. CONCLUSIONS: The CMC consistently provides high volume, backflow resistant CED in tumor infiltrated brain. Co-infusion of a tracer is an essential tool for understanding the delivery characteristics of any CED device. Safety of CED appears to be primarily related to drug concentration and distribution.