Convection-Enhanced Delivery: Neurosurgical Issues

Abstract

Because primary brain tumors treated with surgery, radiation therapy, and chemotherapy have a poor prognosis, this has led investigators to develop new innovative therapies such as targeted toxins. These large molecules do not cross the blood brain barrier and must be delivered into the brain by a technique known as convection-enhanced delivery (CED). When administering these agents, there are a number of pharmacokinetic considerations that must be considered that will directly affect the volume of distribution of the drug being administered and ultimately the therapeutic effect of the agent. A number of different catheter types have been used to perform CED with a hollow fiber design offering several advantages over other variations. Specific parameters have been developed to optimize the placement of the drug delivery catheters in order to enhance drug distribution in the brain. Considerable effort has been expended to identify a reliable way to image the distribution of targeted toxins administered by CED using a combination of magnetic resonance imaging and single photon emission computed tomography. Unfortunately many infusions performed in tumor patients are unsuccessful due to ventricular/subarachnoid leak or pooling of the drug in necrotic tumor tissue. To date, no targeted toxin clinical trial has demonstrated statistically significant clinical results leading to the universal acceptance of this treatment. Other agents such as standard chemotherapy or liposomal preparations have been delivered by CED. Non-neoplastic neurological diseases are being considered for treatment by CED and treating different locations of the brain other that the cerebral hemispheres are under investigation.