title: The European medicines agency review of abiraterone for the treatment of metastatic castration-resistant prostate cancer in adult men after docetaxel chemotherapy and in chemotherapy-naive disease: summary of the scientific assessment of the committee for medicinal products for human use.
abstract: On September 5, 2011, abiraterone was approved in the European Union in combination with prednisone or prednisolone for the treatment of metastatic castration-resistant prostate cancer (CRPC) in adult men whose disease has progressed on or after a docetaxel-based chemotherapy regimen. On December 18, 2012, the therapeutic indication was extended to include the use of abiraterone in combination with prednisone or prednisolone for the treatment of metastatic CRPC in adult men who are asymptomatic or mildly symptomatic after failure of androgen deprivation therapy in whom chemotherapy is not yet clinically indicated. Abiraterone is a selective, irreversible inhibitor of cytochrome P450 17α, an enzyme that is key in the production of androgens. Inhibition of androgen biosynthesis deprives prostate cancer cells from important signals for growth, even in cases of resistance to castration. At the time of European Union approval and in a phase III trial in CRPC patients who had failed at least one docetaxel-based chemotherapy regimen, median overall survival for patients treated with abiraterone was 14.8 months versus 10.9 months for those receiving placebo (hazard ratio, 0.65; 95% confidence interval 0.54-0.77; p < .0001). In a subsequent phase III trial in a similar but chemotherapy-naïve patient population, median radiographic progression-free survival was 16.5 months for patients in the abiraterone treatment arm versus 8.3 months for patients in the placebo arm (hazard ratio, 0.53; 95% confidence interval, 0.45-0.62; p < .0001). Abiraterone was most commonly associated with adverse reactions resulting from increased or excessive mineralocorticoid activity. These were generally manageable with basic medical interventions. The most common side effects (affecting more than 10% of patients) were urinary tract infection, hypokalemia, hypertension, and peripheral edema.
authors: European Medicines Agency, London, United Kingdom;
authors: Iordanis
authors: I
authors: Gravanis
authors: Arantxa Sancho
authors: AS
authors: Lopez
authors: Robert James
authors: RJ
authors: Hemmings
authors: Jorge Camarero
authors: JC
authors: Jiménez
authors: Rocio
authors: R
authors: Garcia-Carbonero
authors: Isabel García
authors: IG
authors: Gallego
authors: Elena Valencia
authors: EV
authors: Giménez
authors: Daniel
authors: D
authors: O'Connor
authors: Rosa
authors: R
authors: Giuliani
authors: Tomas
authors: T
authors: Salmonson
authors: Francesco
authors: F
authors: Pignatti
mesh_terms: D000328:Adult; D000736:Androstenes; D000737:Androstenols / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D017326:Clinical Trials, Phase III as Topic; D018450:Disease Progression; D000077143:Docetaxel; D017277:Drug Approval; D005062:European Union; D006801:Humans; D008297:Male; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D043823:Taxoids / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000736:Androstenes; D000737:Androstenols; D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel; C089740:abiraterone
keywords: Abiraterone; EMA; European Medicines Agency; Prostate cancer
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