Convection Enhanced Drug Delivery of Novel Therapeutic Agents to Malignant Brain Tumors

Sherise      Ferguson; Maciej   S.   Lesniak

doi:10.2174/156720107780362302

Abstract

In spite of conventional treatment modalities which include surgery, chemotherapy, and radiotherapy, the survival rates for patients with malignant gliomas remain disappointing. Successful treatment has been limited by difficulties in delivering therapeutic agents to the central nervous system (CNS). Specifically, drug penetration of the blood brain barrier (BBB) poses a unique and challenging problem in glioma therapy. Recently, however, promising techniques have emerged to circumvent this problem. One such advancement is convection-enhanced delivery (CED). This method was originally introduced and refined in the early 1990s by researchers at the National Institute of Health (NIH) and involves drug infusion under high pressure using intracranial catheters. CED allows for delivery of high concentrations of therapeutic agents directly into brain tumors and surrounding parenchyma. This method eludes the BBB and allows the use of regional drug therapy, while at the same time limiting systemic toxicity. In the present article, we review both the preclinical and clinical studies concerning CED. We also discuss future directions and the potential impact of this modality on the treatment of malignant gliomas.

Keywords: Brain tumor, convection-enhanced delivery, malignant glioma, IL4-PE, IL13-PE38, TransMID, Cotara

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