Modeling Carmustine Diffusion from Gliadel® Wafers in the Brain to Optimize Cancer Treatment and Minimize Damage to Healthy Tissue

Abstract

Gliadel® wafers have been developed to circumvent traditional obstacles in brain cancer treatment. Chemotherapeutic drugs administered intravenously are rendered largely ineffective by the blood-brain barrier. Gliadel wafers can be implanted at the tumor removal site during surgery. These wafers then secrete carmustine (also commonly referred to as BCNU) directly into the remaining tumor tissue. Treatment via Gliadel wafers has been widely successful. However, treatment using carmustine can also cause a variety of serious side effects. Thus, we developed a model to examine the efficacy of Gliadel wafers and improve administration of carmustine to the tumor while minimizing damage to healthy tissue and the occurrence of harmful side effects. The transient diffusion of carmustine from wafers in a realistic, three-dimensional brain geometry was examined using COMSOL®. A zero flux boundary condition was used to represent the blood-brain barrier. Blood flow in the brain and degradation of the drug in both the tumor layer and healthy brain tissue were also considered. Optimal wafer properties were then determined to achieve high carmustine concentrations in the leftover tumor and low concentrations in the healthy tissue.