Blood Brain Barrier Disruption Chemotherapy

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Nancy D. Doolittle, Tulio P. Murillo, and Edward A. Neuwelt

ABSTRACT: The goal of chemotherapy administered in conjunction with blood-brain barrier disruption (BBBD) is maximizing drug delivery to the brain, while preserving neurocognitive function and minimizing systemic toxicity. Translational blood-brain barrier (BBB) pre-clinical and clinical studies at Oregon Health & Science University (OHSU) evaluate the toxicity and antitumor efficacy of chemothera-peutics, chemoprotectants, and monoclonal antibodies (mAbs) as well as novel therapeutics and imaging agents. A current program focus is thiol chemo-protection against the hearing and bone marrow toxicity that is caused by platinum chemotherapy. Thiols may permit increased dose intensity of agents administered in conjunction with BBBD. In the clinic, BBBD has shown promising results in chemo-sensitive brain tumors such as primary central nervous system lymphoma (PCNSL) and offers a new strategy for global delivery of chemotherapy to tumors, such as anaplastic oligodendroglioma and central nervous system metastases. Multi-center clinical trials using BBBD are in progress at centers participating in the BBB Consortium. Current and future clinical studies include delivery of mAbs across the BBB.

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