Convection-enhanced delivery of targeted toxins for malignant glioma

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Abstract
Malignant gliomas represent a difficult treatment challenge for the neuro-oncologist and the neurosurgeon. These tumours continue to be refractory to standard therapies, such as surgery, radiotherapy and conventional chemotherapy, and new therapeutic options are clearly needed. Therefore, investigators have recently taken a new direction and started to engineer compounds such as recombinant cytotoxins, antiangiogenesis factors and genetic delivery vectors. However, these promising new agents are all dependent on an effective distribution method in order to bypass the blood–brain barrier. Convection-enhanced delivery (CED) allows for the administration of targeted toxins and other agents directly into the brain at the site of a tumour via catheters placed with the aid of stereotactic or image-guided surgery. The use of this technique is gaining momentum as a newly accepted treatment modality where little else has produced durable results in the fight against gliomas. Direct intratumoural infusion was first performed in nude mouse flank tumour models of human malignant glioma. After significant testing in preclinical animal studies, this method of delivery was followed by the successful demonstration of in vivo efficacy in Phase I and II clinical trials. Currently, this technique is being used in the investigational setting at academic medical centres where investigators are starting to define the best practice for CED. Fundamental issues in this method of delivery such as rate of infusion, cannula size, infusate concentration and tissue-cannula sealing time shape the current discussion in the literature. Targeted toxin therapy represents one of the newest and most promising treatments for this unfortunate patient population, with proven clinical efficacy administered through CED, which is a novel approach to drug delivery.