CHRONIC CONVECTION ENHANCED DELIVERY (CED) OF TOPOTECAN FOR GLIOBLASTOMA

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DESCRIPTION (provided by applicant): The inability to achieve sufficient intratumoral concentrations of chemotherapeutic drugs in is one of the primary causes of treatment failure in patients with glioblastoma. We have shown in a Phase 1 clinical trial that a topoisomerase inhibitor, topotecan, can be safely and effectively delivered by convection enhanced delivery into patients with recurrent malignant gliomas as a means of overcoming systemic delivery limitations. In this proposal, we will improve this treatment strategy by validating an innovative method for non-invasive monitoring of drug distribution and expanding the duration of infusion by innovating the use of an implantable microinfusion pump. At the conclusion of these studies, the expected outcome will be a novel, measureable strategy to treat patients with recurrent glioblastoma via an implantable pump that can chronically deliver high doses of topotecan into the tumor and surrounding brain to avoid the limitations imposed by conventional systemic delivery. On a broader level, we will have demonstrated, for the first time in humans, the ability to chronically achieve a local-regional distribution of a drug directly into the brain parenchyma.