Convection-enhanced Drug Delivery for Glioblastoma: A Systematic Review Focused on Methodological Differences in the Use of the Convection-enhanced Delivery Method.

Abstract

Glioblastoma (GBM) is a leading cause of brain cancer-related death. The blood–brain barrier (BBB) prevents the transport of most systemic delivered molecules to the brain. This constitutes a major problem in the therapy of brain tumors. In the last decade, numerous different drug-delivery approaches have been developed to overcome the BBB. The objective of this study is to provide an overview of the methodological aspects used in all preclinical and clinical studies published from 2011 to 2016 where convection-enhanced delivery (CED) was used for drug delivery in the treatment of GBM. A systematic review of English articles published in the past 5 years was undertaken using PubMed and Embase. The search terms (brain tumor [MeSH Terms]) AND (CED OR convection enhanced delivery) were used in PubMed and a similar search was carried out in Embase using their “multi-field search.” All studies using CED on an intracranial GBM model were included. The search resulted in 151 hits after duplicates were removed. In total, 30 studies were included in the review. Of these, two publications studied the technical aspects of the CED method. Furthermore, only one study was a clinical study. The research field is focused on preclinical drug development trials and less emphasis is placed on the CED technique itself. However, it is important that future studies focus on establishing optimal protocols for the use of CED in rodents as well as for big brain models to be able to use the CED method in patients with GBM.