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Super selective intra-arterial cerebral infusion of modern chemotherapeutics after blood–brain barrier disruption: where are we now, and where we are going

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A Correction to this article was published on 13 March 2020

This article has been updated

Abstract

Introduction

Intra-arterial (IA) delivery of therapeutic agents across the blood-brain barrier (BBB) is an evolving strategy which enables the distribution of high concentration therapeutics through a targeted vascular territory, while potentially limiting systemic toxicity. Studies have demonstrated IA methods to be safe and efficacious for a variety of therapeutics. However, further characterization of the clinical efficacy of IA therapy for the treatment of brain tumors and refinement of its potential applications are necessary.

Methods

We have reviewed the preclinical and clinical evidence supporting superselective intraarterial cerebral infusion (SSIACI) with BBB disruption for the treatment of brain tumors. In addition, we review ongoing clinical trials expanding the applicability and investigating the efficacy of IA therapy for the treatment of brain tumors.

Results

Trends in recent studies have embraced the use of SSIACI and less neurotoxic chemotherapies. The majority of trials continue to use mannitol as the preferred method of hyperosmolar BBB disruption. Recent preclinical and preliminary human investigations into the IA delivery of Bevacizumab have demonstrated its safety and efficacy as an anti-tumor agent both alone and in combination with chemotherapy.

Conclusion

IA drug delivery may significantly affect the way treatments are delivered to patients with brain tumors, and in particular GBM. With refinement and standardization of the techniques of IA drug delivery, improved drug selection and formulations, and the development of methods to minimize treatment-related neurological injury, IA therapy may offer significant benefits for the treatment of brain tumors.

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Change history

  • 13 March 2020

    The name of author Jason A. Ellis was missing in the intial online publication, and there was a typo in the sixth author's first name. The original article has been corrected.

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  1. Department of Neurosurgery, Zucker School of Medicine At Hofstra/ Northwell Lenox Hill Brain Tumor Center, Lenox Hill Hospital, Northwell Health, New York, NY, USA

    Randy S. D’Amico, Deepak Khatri, Noah Reichman, Nitesh V. Patel, Tamika Wong, Sherese R. Fralin, Mona Li, Jason A. Ellis, Rafael Ortiz, David J. Langer & John A. Boockvar

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D’Amico, R.S., Khatri, D., Reichman, N. et al. Super selective intra-arterial cerebral infusion of modern chemotherapeutics after blood–brain barrier disruption: where are we now, and where we are going. J Neurooncol 147, 261–278 (2020). https://doi.org/10.1007/s11060-020-03435-6

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