4.5 Article

Safety, feasibility, and optimization of intra-arterial mitoxantrone delivery to gliomas

Journal

JOURNAL OF NEURO-ONCOLOGY
Volume 130, Issue 3, Pages 449-454

Publisher

SPRINGER
DOI: 10.1007/s11060-016-2253-3

Keywords

Brain tumor; Chemotherapy; Glioblastoma; Targeted therapy

Funding

  1. National Cancer Institute at the National Institutes of Health [RO1-CA-138643]

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Mitoxantrone is a highly cytotoxic antineoplastic drug, however, its poor penetration of the blood-brain barrier has limited its role in the treatment of brain cancers. We hypothesize that intra-arterial (IA) delivery of mitoxantrone may enhance its capacity for regional brain deposition thus expanding its potential as a brain tumor therapy agent. In this study we assessed the dose-response characteristics as well as the feasibility and safety of mitoxantrone delivery to the brain and specifically to gliomas in a rodent model. We show that delivery optimization utilizing the technique of intra-arterial transient cerebral hypoperfusion (IA-TCH) facilitates achieving the highest peak- and end- brain drug concentrations as compared to intravenous and IA delivery without hypoperfusion. Additionally, we observed significant tumor-specific uptake of mitoxantrone when delivered by the IA-TCH method. No untoward effects of IA-TCH delivery of mitoxantrone were observed. The IA-TCH method is shown to be a safely tolerated and feasible strategy for delivering mitoxantrone to tumors in the glioma model tested. Additional investigation is warranted to determine if IA-TCH delivery of mitoxantrone produces clinically relevant benefit.

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