High-grade glioma is a devastating disease that leaves the majority of its 
victims dead within 2 years. To meaningfully increase survival, a trimodality 
approach of surgery, radiation, and chemotherapy is needed. Carmustine (1,3-bis 
(2-chloroethyl)-1-nitrosourea) is a nitrosourea alkylating agent that exerts its 
antitumor effect by akylating DNA and RNA. Systemic administration of 
nitrosoureas as a single agent or as part of 
procarbazine/3-cyclohexyl-1-nitroso-urea/vincristine has demonstrated little 
efficacy in the treatment of high-grade glioma. The development of carmustine 
wafers (Gliadel((R)) Wafer) as a method for controlled released delivery of 
carmustine from biodegradable polymer wafers enhances the therapeutic ratio by 
fully containing the drug within the confines of the brain tumor environment 
while minimizing systemic toxicities. Preclinical and clinical studies have 
proven the safety and efficacy of Gliadel in the management of glioblastoma. 
From these results, Gliadel is currently approved for use in patients with 
recurrent glioblastoma as an adjunct to surgery and in newly diagnosed patients 
with high-grade glioma as an adjunct to surgery and radiation. Other promising 
advances in the use of locally delivered chemotherapy for CNS malignancies, 
including Gliadel for brain metastases and combination therapies with systemic 
or biologic agents, are discussed.