Summary: Treatment of malignant gliomas represents one of the most formidable challenges in oncology. Despite treatment with surgery, radiation therapy, and chemotherapy, the prognosis remains poor, particularly for glioblastoma, which has a median survival of 12 to 15 months. An important impediment to finding effective treatments for malignant gliomas is the presence of the blood brain barrier, which serves to prevent delivery of potentially active therapeutic compounds. Multiple efforts are focused on developing strategies to effectively deliver active drugs to brain tumor cells. Blood brain barrier disruption and convectionenhanced delivery have emerged as leading investigational delivery techniques for the treatment of malignant brain tumors. Clinical trials using these methods have been completed, with mixed results, and several more are being initiated. In this review, we describe the clinically available methods used to circumvent the blood brain barrier and summarize the results to date of ongoing and completed clinical trials. Key Words: Convection-enhanced delivery, blood brain barrier disruption, brain neoplasm, drug delivery system.

Gliomas are one of the most lethal forms of cancer. The poor prognosis associated with these malignant primary brain tumors treated with surgery, radiotherapy and chemotherapy has led researchers to develop new strategies for cure. Interstitial drug delivery has been the most appealing method for the treatment of primary brain tumors because it provides the most direct method of overcoming the barriers to tumor drug delivery. By administering therapeutic agents directly to the brain interstitium and, more specifically, to tumor-infiltrated parenchyma, one can overcome the elevated interstitial pressure produced by brain tumors. Convection-enhanced delivery (CED) has emerged as a leading investigational delivery technique for the treatment of brain tumors. Clinical trials utilizing these methods have been completed, with mixed results, and several more are being initiated. However, the potential efficacy of these drugs may be limited by ineffective tissue distribution. The development of computer models/algorithms to predict drug distribution, new catheter designs, and utilization of tracer models and nanocarriers have all laid the groundwork for the advancement of CED. In this review, we summarize the recent past of the clinical trials utilizing CED and discuss emerging technologies that will shape future CED trials.