Bypassing the Blood-Brain Barrier to Treat Brain Cancer: A Systematic Review of the Efficacy of Carmustine Wafer Implant Therapy

Abstract

Introduction: Gliomas are neoplasms of the central nervous system (CNS). Despite aggressive treatment, median survival of malignant tumors remains poor at 12 - 18 months. Newer treatments allow delivery of therapeutic substances across the selectively permeable blood-brain barrier (BBB). This allows for chemotherapeutics to more easily reach their target location in the CNS. Drug eluting wafers made up of carmustine can be placed in the surgical resection cavity of a tumor and clinical trials to date have demonstrated their utility. Hypothesis: Bypassing the BBB to allow greater accumulation of chemotherapeutics in the CNS will improve clinical outcomes in glioma patients. Methods: Studies from medical literature databases describing trials using carmustine wafers implanted after glioma resection were obtained. To test our hypothesis, the available data using this therapy was compared to current first line treatment data for glioma as described by Stupp and colleagues. The inclusion criterion for efficacy analysis was histopathologically confirmed primary glioma. Exclusion criteria included presence of metastasis or pediatric tumors. Results: 10 studies describing wafer therapy use were initially gathered, encompassing over 500 patients. 6 studies met criteria for treatment efficacy analysis. 4 of 6 (75%) trials exhibited significant survival advantage as compared to control treatment. Furthermore, 3 of the 4 (75%) studies showing significance also demonstrated equal or higher percent increase in overall survival from control as compared to data generated from current first line therapy. Conclusion: Treatments bypassing the BBB are not currently standard-of-care for patients with glioma. We uncovered that most trials using carmustine implants post tumor resection describe increased overall survival, however in specific cohorts. Diverting the BBB in general may also have fewer side effects in contrast to classical routes of therapy. Future work is needed to develop similar therapeutics that improve outcomes in all age, gender, and prognostic risk factor populations.