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

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 demonstrate...

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Bibliographic Details
Published in:Journal of neuro-oncology 2020-04, Vol.147 (2), p.261-278
Main Authors: D’Amico, Randy S., Khatri, Deepak, Reichman, Noah, Patel, Nitesh V., Wong, Tamika, Fralin, Sherese R., Li, Mona, Ellis, Jason A., Ortiz, Rafael, Langer, David J., Boockvar, John A.
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - administration & dosage
Bevacizumab
Blood-brain barrier
Blood-Brain Barrier - drug effects
Brain cancer
Brain Neoplasms - drug therapy
Brain tumors
Chemotherapy
Clinical trials
Drug delivery
Drug Delivery Systems
Glioma
Humans
Infusions, Intra-Arterial - methods
Mannitol
Medicine
Medicine & Public Health
Monoclonal antibodies
Neoplasm Recurrence, Local - prevention & control
Neurology
Neurotoxicity
Oncology
Osmotic pressure
Standardization
Targeted cancer therapy
Topic Review
Treatment Outcome
Tumors
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Summary: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.
ISSN:0167-594X
1573-7373
DOI:10.1007/s11060-020-03435-6