Abstract | BACKGROUND: OBJECTIVE: DESIGN, SETTING, AND PARTICIPANTS: OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Changes in prostate-specific antigen (PSA) levels and progression-free survival were used to determine the activity of cabazitaxel treatment. Cell proliferation, immunofluorescence, and AR transactivation assay were used in enzalutamide-resistant models. RESULTS AND LIMITATIONS: A total of 79 patients who had progressive mCRPC after docetaxel (median: 8 cycles; range: 4-12 mo), and AA (median: 4.8 mo; range:1-55 mo) received cabazitaxel 25mg/m(2) every 3 weeks (median: 6 cycles; range:1-15 cycles). A PSA decline ≥30% was achieved in 48 patients (62%; 95% confidence interval [CI], 51-73), and a decline ≥50% was achieved in 28 patients (35%; 95% CI, 25-47). The median progression-free survival and overall survival were 4.4 and 10.9 mo, respectively. In vitro, cabazitaxel decreased cell viability in both enzalutamide-sensitive and enzalutamide-resistant prostate cancer cells within the same range of concentrations. PC3, an AR-negative cell line, exhibited similar sensitivity to cabazitaxel. CONCLUSIONS:
Cabazitaxel and AR-pathway inhibitors are not cross-resistant. Preclinical data suggest that cabazitaxel activity does not act mainly through AR axis inhibition. PATIENT SUMMARY:
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Authors | Nader Al Nakouzi, Sylvestre Le Moulec, Laurence Albigès, Chris Wang, Philippe Beuzeboc, Marine Gross-Goupil, Thibault de La Motte Rouge, Aline Guillot, Dorota Gajda, Christophe Massard, Martin Gleave, Karim Fizazi, Yohann Loriot |
Journal | European urology
(Eur Urol)
Vol. 68
Issue 2
Pg. 228-35
(Aug 2015)
ISSN: 1873-7560 [Electronic] Switzerland |
PMID | 24837187
(Publication Type: Journal Article, Multicenter Study)
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Copyright | Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved. |
Chemical References |
- AR protein, human
- Androgen Antagonists
- Androstenes
- Benzamides
- Nitriles
- Receptors, Androgen
- Taxoids
- Docetaxel
- Phenylthiohydantoin
- cabazitaxel
- enzalutamide
- KLK3 protein, human
- Kallikreins
- Prostate-Specific Antigen
- abiraterone
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Topics |
- Aged
- Aged, 80 and over
- Androgen Antagonists
(adverse effects, therapeutic use)
- Androstenes
(adverse effects, therapeutic use)
- Antineoplastic Combined Chemotherapy Protocols
(adverse effects, therapeutic use)
- Benzamides
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Cell Survival
(drug effects)
- Disease-Free Survival
- Docetaxel
- Dose-Response Relationship, Drug
- Drug Resistance, Neoplasm
- France
- Humans
- Kallikreins
(blood)
- Kaplan-Meier Estimate
- Male
- Middle Aged
- Molecular Targeted Therapy
- Nitriles
- Phenylthiohydantoin
(adverse effects, analogs & derivatives, therapeutic use)
- Prostate-Specific Antigen
(blood)
- Prostatic Neoplasms, Castration-Resistant
(drug therapy, metabolism, mortality, pathology)
- Receptors, Androgen
(drug effects, metabolism)
- Retrospective Studies
- Signal Transduction
(drug effects)
- Taxoids
(adverse effects, therapeutic use)
- Time Factors
- Treatment Outcome
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