Convection-enhanced delivery in the treatment of malignant glioma

Abstract

Despite advancements in glioma therapy, median survival remains low because of rapid post-resection recurrence. A regional method of drug delivery to address local invasion may improve clinical outcomes. Convection-enhanced delivery (CED) is a novel therapy that allows distribution of substances throughout the interstitium via positive-pressure infusion. Studies using various agents have investigated the parameters that affect CED including infusion rate, cannula size, infusion volume, extracellular space, particle characteristics and tumor tissue structure. We review models of small animal glioma that have been successfully treated using different substances administered through CED, particularly our favorable results using topotecan in a C6 rat glioma model. We also review Phase I/II trials utilizing CED which have shown promising response rates and acceptable safety profiles. Future studies should include prospective clinical trials and investigation of novel antitumor agents that are ineffective with systemic delivery. Development of a large animal glioma model would enhance pre-clinical investigation of CED. Clinically, methods to monitor distribution of therapeutic agents and real-time patient response should likewise be explored.