Results of a Pilot Trial of Infusion Rate Escalation During Convection-Enhanced Delivery of Topotecan with a Multiport Catheter.

Abstract

Volume of distribution (Vd) during convection-enhanced delivery is impacted by the physical characteristics of the tissue being treated. For glioblastoma, Vd is substantially higher in noncontrast-enhancing tumor than in contrast-enhancing tumor due to higher infusate efflux in enhancing tumor. We hypothesized that increasing the infusion rate could overcome the infusate efflux rate in enhancing tumor to improve the Vd to volume of infusion ratio and provide better tumor coverage. A single-center, institutional review board-approved pilot study was conducted to perform rate-escalated delivery of Topotecan with gadolinium-DTPA to contrast-enhancing recurrent high-grade glioma. A single Cleveland Multiport Catheter was surgically placed into enhancing tumor and then a 4-hour infusion was performed with real-time magnetic resonance imaging visualization. Intrapatient and interpatient rate escalation was performed. Three patients with recurrent high-grade glioma were enrolled and treated. The initial infusion rate for patient 1 was 5 μL/minute per microcatheter (4 total) and the final infusion rate for the third patient was 20 μL/minute per microcatheter. We observed partial backflow at this rate and therefore did not escalate higher. There was coverage of both enhancing and nonenhancing tumor in all cases, and the Vd/volume of infusion ratio ranged from 0.7 to 1.3. The patients tolerated the treatments well; there were no common terminology criteria for adverse events Grade 3 or higher treatment-related adverse events. The higher efflux rate associated with contrast-enhancing tumor tissue can be overcome with sufficient infusion rate escalation. Increasing the rate of infusion can allow for larger Vd into enhancing tumor tissue.