Future of convection-enhanced delivery in the treatment of brain tumors

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.