Efficacy of cabazitaxel in mouse models of pediatric brain tumors.

Neuro Oncol

Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington (E.G., S.D., A.R., J.O.); Department of Radiology, University of Washington, Seattle, Washington (D.L., K.Y., J.P., H.E.); Sanofi Oncology, Global Oncology Division, Cambridge, Massachusetts 02142 (D.B.); Oncology/Translational and Experimental Medicine, Sanofi Inc, Vitry sur Seine, France (P.V.).

Published: January 2015

Background: There is an unmet need in the treatment of pediatric brain tumors for chemotherapy that is efficacious, avoids damage to the developing brain, and crosses the blood-brain barrier. These experiments evaluated the efficacy of cabazitaxel in mouse models of pediatric brain tumors.

Methods: The antitumor activity of cabazitaxel and docetaxel were compared in flank and orthotopic xenograft models of patient-derived atypical teratoid rhabdoid tumor (ATRT), medulloblastoma, and central nervous system primitive neuroectodermal tumor (CNS-PNET). Efficacy of cabazitaxel and docetaxel were also assessed in the Smo/Smo spontaneous mouse medulloblastoma tumor model.

Results: This study observed significant tumor growth inhibition in pediatric patient-derived flank xenograft tumor models of ATRT, medulloblastoma, and CNS-PNET after treatment with either cabazitaxel or docetaxel. Cabazitaxel, but not docetaxel, treatment resulted in sustained tumor growth inhibition in the ATRT and medulloblastoma flank xenograft models. Patient-derived orthotopic xenograft models of ATRT, medulloblastoma, and CNS-PNET showed significantly improved survival with treatment of cabazitaxel.

Conclusion: These data support further testing of cabazitaxel as a therapy for treating human pediatric brain tumors.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4483053PMC
http://dx.doi.org/10.1093/neuonc/nou163DOI Listing

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