Abstract | PURPOSE: While first-generation taxanes are valuable treatment options for many solid tumors, they are limited by an inability to cross the blood-brain barrier (BBB) and by limited efficacy in pediatric patients. Following promising preclinical data for the next-generation taxane cabazitaxel, including activity in tumor models fully sensitive, poorly sensitive or insensitive to docetaxel, and its ability to cross the BBB, further preclinical studies of cabazitaxel relevant to these two clinical indications were performed. METHODS: RESULTS:
Cabazitaxel penetrated rapidly in the brain, with a similar brain-blood radioactivity exposure relationship across different animal species. In intracranial human glioblastoma models, cabazitaxel demonstrated superior activity to docetaxel both at early (before BBB disruption) and at advanced stages, consistent with enhanced brain penetration. Compared with similar dose levels of docetaxel, cabazitaxel induced significantly greater tumor growth inhibition across six pediatric tumor models and more tumor regressions in five of the six models. Therapeutic synergism was observed between cisplatin and cabazitaxel, regardless of administration sequence. CONCLUSIONS: These preclinical data suggest that cabazitaxel could be an effective therapy in CNS and pediatric tumors, supporting ongoing clinical evaluation in these indications.
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Authors | D Sémiond, S S Sidhu, M-C Bissery, P Vrignaud |
Journal | Cancer chemotherapy and pharmacology
(Cancer Chemother Pharmacol)
Vol. 72
Issue 3
Pg. 515-28
(Sep 2013)
ISSN: 1432-0843 [Electronic] Germany |
PMID | 23820961
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents
- Taxoids
- cabazitaxel
- Cisplatin
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Topics |
- Animals
- Antineoplastic Agents
(administration & dosage, pharmacokinetics, pharmacology)
- Antineoplastic Combined Chemotherapy Protocols
(administration & dosage, pharmacokinetics, pharmacology)
- Blood-Brain Barrier
(metabolism)
- Brain
(metabolism)
- Brain Neoplasms
(drug therapy, pathology)
- Child, Preschool
- Cisplatin
(administration & dosage)
- Dogs
- Drug Synergism
- Female
- Humans
- Male
- Mice
- Mice, Inbred BALB C
- Neoplasm Staging
- Neoplasms
(drug therapy, pathology)
- Neoplasms, Experimental
(drug therapy, pathology)
- Rats
- Rats, Sprague-Dawley
- Species Specificity
- Taxoids
(administration & dosage, pharmacokinetics, pharmacology)
- Tissue Distribution
- Xenograft Model Antitumor Assays
- Young Adult
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