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Abstract
Although most prostate cancers initially respond to castration with luteinizing hormone- releasing analogues or bilateral orchiectomy, progression eventually occurs. Based on the exciting results of several randomized controlled trials (RCTs), it seems that patients with metastatic castration-resistant prostate cancer (mCRPC) might benefit more from treatment withabiraterone. Therefore we conducted a systematic review to evaluate the efficacy and toxicity of abiraterone in the treatment of mCRPC. Literature was searched from Embase, PubMed, Web of Science, and Cochrane Library up to July, 2013. Quality of the study was evaluated according to the Cochrane's risk of bias of randomized controlled trial (RCT) tool, then the Grading of Recommendations Assessment, Development and Evaluation (GRADE) System was used to rate the level of evidence. Stata 12.0 was used for statistical analysis. Summary data from RCTs comparing abiraterone plus prednisone versus placebo plus prednisone for mCRPC were meta-analyzed. Pooled hazard ratios (HRs) for overall survival (OS), radiographic progression-free survival (RPFS) and time to PSA progression (TTPP); Pooled risk ratios (RR) for PSA response rate, objective response rate and adverse event were calculated. Ten trials were included in the systematic review; Data of 2,283 patients (1,343 abiraterone; 940 placebo) from two phase 3 trials: COU-AA-301 and COU-AA-302 were meta-analyzed. Compared with placebo, abiraterone significantly prolonged OS (HR, 0.74; 95% confidence interval [CI], 0.66 to 0.84), RPFS (HR, 0.59; 95% CI, 0.48 to 0.74) and time to PSA progression (HR, 0.55; 95% CI, 0.43 to 0.70); it also significantly increased PSA response rate (RR, 3.63; 95% CI, 1.72 to 7.65) and objective response rate (RR, 3.05; 95% CI, 1.51 to 6.15). This meta-analysis suggested that the adverse events caused by abiraterone are acceptable and can be controlled. CONCLUTIOS: Abiraterone significantly prolonged OS, RPFS and time to progression patients with mCRPC, regardless of prior chemotherapy or whether chemotherapy-naive, and no unexpected toxicity was evident. Abiraterone can serve as a new standard therapy for mCRPC.
Highlights
Most prostate cancers initially respond to castration with luteinizing hormonereleasing analogues or bilateral orchiectomy, progression eventually occurs
The median TTPP on abiraterone acetate alone for phase II patients was 225 days; 50% decline in prostate-specific antigen (PSA) was confirmed in 22 patients: including 14 of 31 ketoconazole-naïve, 7 of 27 ketoconazole-pretreated patients; Partial responses were seen in 4 of 22 patients; Median time to PSA progression was 169 days; CTC conversions from >5 to < 5 were noted in 10 of 29 patients; Main adverse events were grade 1 to 2, no grade 4 events were seen
The results showed that PSA response rate was significantly increased in abiraterone acetate plus prednisone treatment group compared with group than in the prednisone alone group; There was no significant difference in fatigue, back pain, nausea, pain in extremity, constipation, and bone pain among the grade 1 to 4 adverse events in the two groups (Figure 5)
Summary
Prostate cancer is the most common malignant neoplasm and a leading cause of cancer mortality in men in the Western world. Most men initially respond to castration with treatment of luteinizing hormonereleasing analogues or bilateral orchiectomy, progression eventually occurs, and the median overall survival after chemotherapy is consistently less than 2 years in patients with metastatic castration-resistant prostate cancer (mCRPC) (Crawford et al, 1989). A phase 3 trial on abiraterone acetate plus prednisone versus placebo plus prednisone in men with mCRPC who have not received prior chemotherapy has been completed, the results showed that the median radiographic progression-free survival was 16.5 months with abiraterone-prednisone and 8.3 months with prednisone alone, and overall survival was significantly improved with abiraterone-prednisone too (Ryan et al, 2012). This systematic review and meta-analysis was designed, with the aim to fully evaluate the efficacy and toxicity of abiraterone for metastatic castration-resistant prostate cancer, and we comprehensively appraised the quality of evidence and recommended the evidence with GRADE to facilitate clinical decision-making
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