Serum androgens as prognostic biomarkers in castration-resistant prostate cancer: results from an analysis of a randomized phase III trial

Autor: Charles J. Ryan, T. Kheoh, Russell P. Grant, Eric J. Small, Arturo Molina, C. M. Haqq, Jinhui Li, Howard I. Scher, Johann S. de Bono
Rok vydání: 2013
Předmět:
Oncology
Male
Cancer Research
Aging
medicine.medical_treatment
Abiraterone Acetate
Gastroenterology
Prostate cancer
chemistry.chemical_compound
Testosterone
Cancer
Prostate Cancer
Hazard ratio
Pain Research
Abiraterone acetate
ORIGINAL REPORTS
Prognosis
Quartile
Docetaxel
6.1 Pharmaceuticals
Androgens
Chronic Pain
medicine.drug
Urologic Diseases
medicine.medical_specialty
Randomization
medicine.drug_class
Urology
Clinical Sciences
Oncology and Carcinogenesis
Liquid-Liquid Extraction
Dehydroepiandrosterone sulfate
Double-Blind Method
Internal medicine
medicine
Humans
Oncology & Carcinogenesis
Chemotherapy
Proportional hazards model
business.industry
Evaluation of treatments and therapeutic interventions
Prostatic Neoplasms
medicine.disease
Androgen
Androstadienes
Endocrinology
chemistry
Prednisone
business
Orchiectomy
Zdroj: Journal of clinical oncology : official journal of the American Society of Clinical Oncology, vol 31, iss 22
ISSN: 1527-7755
Popis: Purpose In the phase III study COU-AA-301, abiraterone acetate (AA) plus prednisone (P) prolonged overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) after docetaxel administration. In this article, we investigate the relationship between baseline serum androgen (SA) levels and OS. Patients and Methods COU-AA-301 is a randomized, double-blind study of AA (1,000 mg every day) plus P (5 mg by mouth twice daily; n = 797) versus P alone (n = 398). Randomization was stratified by Eastern Cooperative Oncology Group performance status (0 to 1 v 2), pain (Brief Pain Inventory-Short Form over past 24 hours: 4 to 10, present; v 0 to 3, absent), prior chemotherapy (1 v 2), and progression (prostate-specific antigen v radiographic). Association of baseline SA (testosterone, androstenedione, dehydroepiandrosterone sulfate), was measured by ultrasensitive liquid-liquid extraction or protein precipitation and two-dimensional liquid chromatography coupled to mass spectrometry, with OS determined by bivariate and multivariable Cox models. OS was examined with SA as greater than median and less than or equal to the median. Results Median survival increased with each quartile increase in testosterone level regardless of treatment arm. SA levels at baseline strongly associated with survival (P < .0001) in bivariate and multivariable analyses. Longer survival was observed for patients with SA above median compared with below median in both the AA and P arms (eg, testosterone, AA; hazard ratio, 0.64; 95% CI, 0.53 to 0.77; P < .0001). Treatment with AA led to longer survival versus P alone in the above- or below-median group for all androgens. Conclusion SA, measured with a novel ultrasensitive assay in COU-AA-301, is prognostic for OS and may be useful for risk stratification in mCRPC clinical trials.
Databáze: OpenAIRE
Externí odkaz: