Abstract 5055: Efficacy of cabazitaxel in mouse models of pediatric brain tumors.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Successful treatment of pediatric brain tumorsis 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 barrieris a large hurdle in effectively treating brain tumors, particularly when there is a need, as with very young patients, to avoid radiation therapy. Cabazitaxelis a promising taxanederivative shown to effectively kill tumor cells in pre-clinical in vitro and in vivo experiments. Similar to docetaxel, cabazitaxelhas 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, cabazitaxelhas shown efficacy in docetaxelresistant tumors. The experiments presented here, tested the relative efficacy of cabazitaxeland docetaxelin mouse models of pediatric brain tumors. A spontaneous mouse model of medulloblastomadriven by Smo activation was evaluated by magnetic resonance imaging for tumor growth and blood brain barrierintegrity before and after treatment with cabazitaxelor docetaxel. Efficacy of cabazitaxeland docetaxelagainst patient-derived pediatric brain tumorswas tested in flank and orthotopic xenograft models of medulloblastoma, sPNET, ATRT, and ependymoma. We observed regression in some flank xenograft tumors after treatment with cabazitaxelor docetaxel, with evidence of superior action of cabazitaxel. These data support further testing of cabazitaxelas 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 cabazitaxelin 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