A Review of Therapeutic Agents Given by Convection-Enhanced Delivery for Adult Glioblastoma

Abstract

Glioblastoma remains a devastating disease with a bleak prognosis despite continued research and numerous clinical trials. Convection-enhanced delivery offers researchers and clinicians a platform to bypass the blood-brain barrier and administer drugs directly to the brain parenchyma. While not without significant technological challenges, convection-enhanced delivery theoretically allows for a wide range of therapeutic agents to be delivered to the tumoral space while preventing systemic toxicities. This article provides a comprehensive review of the antitumor agents studied in clinical trials of convection-enhanced delivery to treat adult high-grade gliomas. Agents are grouped by classes, and preclinical evidence for these agents is summarized, as is a brief description of their mechanism of action. The strengths and weaknesses of each clinical trial are also outlined. By doing so, the difficulty of untangling the efficacy of a drug from the technological challenges of convection-enhanced delivery is highlighted. Finally, this article provides a focused review of some therapeutics that might stand to benefit from future clinical trials for glioblastoma using convection-enhanced delivery.

Keywords: blood-brain barrier; convection-enhanced delivery; drug delivery; glioblastoma; high-grade glioma; volume of distribution.

Figure 1

This figure depicts the average IC₅₀’s in micromolar of select compounds against glioblastoma cell lines. Bars represent the natural logarithm of the arithmetic average of IC₅₀’s in micromolar across 20+ GBM cell lines present in the Cancerrxgene database, an online database of cell line sensitivities to various drugs. Blue bars represent the compounds used in CED clinical trials. Red bars represent the compounds mentioned in this review that have not yet reached clinical trial via CED.