Abstract | BACKGROUND: METHODS: Between April 28, 2009, and June 23, 2010, patients with progressive, metastatic castration-resistant prostate cancer were enrolled into a multinational, double-blind, placebo-controlled trial. Patients were eligible if they were asymptomatic (score of 0 or 1 on item three of the Brief Pain Inventory Short Form [BPI-SF] questionnaire) or mildly symptomatic (score of 2 or 3) and had not previously received chemotherapy. Patients were randomly assigned (1:1) to receive oral abiraterone (1 g daily) plus prednisone (5 mg twice daily) or placebo plus prednisone in continuous 4-week cycles. Pain was assessed with the BPI-SF questionnaire, and health-related quality of life (HRQoL) with the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire. We analysed data with prespecified criteria for clinically meaningful pain progression and deterioration in HRQoL. All patients who underwent randomisation were included in analyses. FINDINGS: 1088 patients underwent randomisation: 546 were assigned to abiraterone plus prednisone and 542 to placebo plus prednisone. At the time of the second prespecified interim analysis, median follow-up was 22·2 months (IQR 20·2-24·8). Median time to progression of mean pain intensity was longer in patients assigned to abiraterone plus prednisone (26·7 months [95% CI 19·3-not estimable]) than in those assigned to placebo plus prednisone (18·4 months [14·9-not estimable]; hazard ratio [HR] 0·82, 95% CI 0·67-1·00; p=0·0490), as was median time to progression of pain interference with daily activities (10·3 months [95% CI 9·3-13·0] vs 7·4 months [6·4-8·6]; HR 0·79, 95% CI 0·67-0·93; p=0·005). Median time to progression of worst pain was also longer with abiraterone plus prednisone (26·7 months [95% CI 19·4-not estimable]) than with placebo plus prednisone (19·4 months [16·6-not estimable]), but the difference was not significant (HR 0·85, 95% CI 0·69-1·04; p=0·109). Median time to HRQoL deterioration was longer in patients assigned to abiraterone plus prednisone than in those assigned to placebo plus prednisone as assessed by the FACT-P total score (12·7 months [95% CI 11·1-14·0] vs 8·3 months [7·4-10·6]; HR 0·78, 95% CI 0·66-0·92; p=0·003) and by the score on its prostate-cancer-specific subscale (11·1 months [8·6-13·8] vs 5·8 months [5·5-8·3]; HR 0·70, 95% CI 0·60-0·83; p<0·0001). INTERPRETATION:
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Authors | Ethan Basch, Karen Autio, Charles J Ryan, Peter Mulders, Neal Shore, Thian Kheoh, Karim Fizazi, Christopher J Logothetis, Dana Rathkopf, Matthew R Smith, Paul N Mainwaring, Yanni Hao, Thomas Griffin, Susan Li, Michael L Meyers, Arturo Molina, Charles Cleeland |
Journal | The Lancet. Oncology
(Lancet Oncol)
Vol. 14
Issue 12
Pg. 1193-9
(Nov 2013)
ISSN: 1474-5488 [Electronic] England |
PMID | 24075621
(Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Meta-Analysis, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2013 Elsevier Ltd. All rights reserved. |
Chemical References |
- Androstadienes
- Abiraterone Acetate
- Prednisone
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Topics |
- Abiraterone Acetate
- Activities of Daily Living
- Androstadienes
(administration & dosage)
- Antineoplastic Combined Chemotherapy Protocols
(therapeutic use)
- Australia
- Canada
- Cost of Illness
- Disease Progression
- Double-Blind Method
- Drug Administration Schedule
- Europe
- Humans
- Kaplan-Meier Estimate
- Male
- Pain
(diagnosis, etiology, prevention & control)
- Pain Measurement
- Prednisone
(administration & dosage)
- Proportional Hazards Models
- Prospective Studies
- Prostatic Neoplasms, Castration-Resistant
(complications, drug therapy, pathology)
- Quality of Life
- Surveys and Questionnaires
- Time Factors
- Treatment Outcome
- United States
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