Abstract
Abstract Successful treatment of pediatric brain tumors is limited by significant long-term toxicities associated with surgery and radiation therapy on the developing central nervous system There is an unmet need for chemotherapy with improved efficacy in difficult to treat tumors, such as supratentorial primitive neuroectodermal tumors (sPNET) and atypical teratoid/rhabdoid tumors (ATRT), as well as diagnoses that currently have good long-term survival, such as medulloblastoma. Overcoming the blood brain barrier is a large hurdle in effectively treating brain tumors, particularly when there is a need, as with very young patients, to avoid radiation therapy. Cabazitaxel is a promising taxane derivative shown to effectively kill tumor cells in pre-clinical in vitro and in vivo experiments. Similar to docetaxel, cabazitaxel has favorable drug properties and a manageable safety profile in patients with advanced solid tumors, with the advantage of being able to cross the blood brain barrier. Additionally, cabazitaxel has shown efficacy in docetaxel resistant tumors. The experiments presented here, tested the relative efficacy of cabazitaxel and docetaxel in mouse models of pediatric brain tumors. A spontaneous mouse model of medulloblastoma driven by Smo activation was evaluated by magnetic resonance imaging for tumor growth and blood brain barrier integrity before and after treatment with cabazitaxel or docetaxel. Efficacy of cabazitaxel and docetaxel against patient-derived pediatric brain tumors was tested in flank and orthotopic xenograft models of medulloblastoma, sPNET, ATRT, and ependymoma. We observed regression in some flank xenograft tumors after treatment with cabazitaxel or docetaxel, with evidence of superior action of cabazitaxel. These data support further testing of cabazitaxel as a therapy to treat human pediatric brain tumors. This work has been funded by Sanofi Inc. Citation Format: James M. Olson, Emily Girard, Sally Ditzler, Andrew Richards, Doonhoon Lee, Patricia Vrignaud. Efficacy of cabazitaxel in mouse models of pediatric brain tumors. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5055. doi:10.1158/1538-7445.AM2013-5055
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