title: Intraarterial drug delivery for glioblastoma mutiforme: Will the phoenix rise again?
abstract: Intraarterial (IA) drug delivery is a physiologically appealing strategy as drugs are widely distributed throughout the tumor capillary network and high regional tissue concentrations can be achieved with low total doses. IA treatment of glioblastoma multiforme (GBM) has been attempted since the 1950s but success has been elusive. Although IA treatments have been embraced for the treatment of retinoblastoma and advanced liver cancers, this has not been the case for GBM. The development of IA drug delivery for the treatment of brain cancer over the last several decades reveals a number of critical oversights. For example, very few studies took into consideration the underlying hydrodynamic factors. Therapeutic failures were often blamed on an inability to penetrate the blood brain barrier or on the streaming of drugs. Similarly, there were few methods to investigate the ultra-fast pharmacokinetics of IA drugs. Despite past failures, clinical interest in IA drugs for the treatment of GBM persists. The advent of modern imaging methods along with a better understanding of hydrodynamics factors, better appreciation of the complex morphology of GBM, improved drug selection and formulations, and development of methods to minimize treatment-related neurological injury, promise to considerably advance the application of IA drugs for GBM treatment. There are several clinical trials with IA treatments in the National Trial Registry that are actively recruiting patients. This review of IA drug delivery for GBM treatment is therefore timely and is intended to assess how this method of drug delivery could be better applied to future treatments.
authors.affiliation: Department of Anesthesiology, College of Physicians and Surgeons of Columbia University, 630 West 168th Street, P&S Box 46, New York, NY, 10032, USA. sj121@cumc.columbia.edu.
authors.forename: Shailendra
authors.initials: S
authors.lastname: Joshi
authors.affiliation: Department of Neurological Surgery, Columbia University Medical Center, New York, NY, USA. jae2109@columbia.edu.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Ellis
authors.affiliation: Department of Anesthesiology, College of Physicians and Surgeons of Columbia University, 630 West 168th Street, P&S Box 46, New York, NY, 10032, USA.
authors.forename: Eugene
authors.initials: E
authors.lastname: Ornstein
authors.affiliation: Department of Neurological Surgery, Columbia University Medical Center, New York, NY, USA.
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Bruce
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001932:Brain Neoplasms / Q000188:drug therapy*; D016503:Drug Delivery Systems; D005909:Glioblastoma / Q000188:drug therapy*; D006801:Humans; D007261:Infusions, Intra-Arterial
chemical_list: D000970:Antineoplastic Agents
keywords: Blood–brain barrier; Brain tumor; Chemotherapy; Glioblastoma multiforme; Glioma; Intraarterial