Cabazitaxel Remains Active in Patients Progressing After Docetaxel Followed by Novel Androgen Receptor Pathway Targeted Therapies

Autor: Yohann Loriot, Aline Guillot, Nader Al Nakouzi, Christophe Massard, Chris Wang, Laurence Albiges, Philippe Beuzeboc, Marine Gross-Goupil, Dorota Gajda, Sylvestre Le Moulec, Martin E. Gleave, Karim Fizazi, Thibault De La Motte Rouge
Rok vydání: 2015
Předmět:
Male
Oncology
Time Factors
medicine.medical_treatment
Docetaxel
Kaplan-Meier Estimate
Prostate cancer
chemistry.chemical_compound
Antineoplastic Combined Chemotherapy Protocols
Molecular Targeted Therapy
Aged
80 and over
Abiraterone acetate
Middle Aged
Prostatic Neoplasms
Castration-Resistant
Treatment Outcome
Receptors
Androgen
Cabazitaxel
Benzamides
Hormonal therapy
Androstenes
Kallikreins
Taxoids
France
Signal Transduction
medicine.drug
medicine.medical_specialty
Cell Survival
Urology
Disease-Free Survival
Andrology
Cell Line
Tumor
Internal medicine
Nitriles
Phenylthiohydantoin
medicine
Humans
Enzalutamide
Aged
Cell Proliferation
Retrospective Studies
Chemotherapy
Dose-Response Relationship
Drug
business.industry
Androgen Antagonists
Prostate-Specific Antigen
medicine.disease
chemistry
Drug Resistance
Neoplasm
business
Progressive disease
Zdroj: European Urology. 68:228-235
ISSN: 0302-2838
DOI: 10.1016/j.eururo.2014.04.015
Popis: Background Cabazitaxel, abiraterone acetate (AA), and enzalutamide have been approved for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) following docetaxel chemotherapy. Whether taxanes and next-generation androgen receptor (AR) axis inhibitors are cross-resistant or not is a subject of debate. Objective To evaluate the antitumour activity of cabazitaxel in mCRPC pretreated with abiraterone or enzalutamide. Design, setting, and participants The antitumour activity of cabazitaxel was assessed in patients with mCRPC and progressive disease after treatment with docetaxel and AA. In parallel, cabazitaxel antitumour activity was studied in enzalutamide-resistant models. 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 The antitumour activity of cabazitaxel, a chemotherapy agent, was studied in prostate cancer resistant to conventional hormonal therapy and to more recent endocrine therapies (abiraterone or enzalutamide). Cabazitaxel retained anticancer activity in more than half of the cases.
Databáze: OpenAIRE
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