Abstract
e15140 Background: CYP17 inhibitor abiraterone acetate has been used for the treatment of patients with metastatic castration-refractory prostate cancer (CRPC). Hypertension, hypokalemia and edema are the major side effects associated with its use, and may be secondary to the excess of mineralocorticoids due to CYP17 inhibition. We performed a systematic review and meta-analysis of published clinical trials to determine the effect of abiraterone on the development of these side effects. Methods: Databases including Pubmed (July, 1966 to July, 2011), Web of Science, and abstracts presented at the American Society of Clinical Oncology meetings from 2008 to 2011 were searched to identify relevant studies. Eligible studies were prospective clinical trials of patients with prostate cancer receiving abiraterone acetate at the starting dose of 1,000 mg daily with available data on hypertension, hypokalemia and edema. Incidence and relative risk (RR) were calculated using a random-effects or fixed-effects model. Results: A total of seven studies including 1,387 patients with CRPC were selected for analysis. The incidences of all-grade hypertension, hypokalemia, and edema were 13.3% (95% CI: 8.3 to 20.5%), 31.4 % (95% CI: 12.5-59.5%), and 23.4 % (95% CI: 15.6-33.5%) respectively. The incidences of high-grade (grade 3 and above) toxicity were low, with a rate of 3.6% (95% CI: 2.6-5.1%), 2.8 % (95% CI: 0.9 to 8.2%), and 2.1% (95%CI: 1.3-3.2%) for hypertension, hypokalemia, and edema respectively. The risk of hypertension and edema did not change with and without the addition of prednisone (p=0.48 and p=0.40, respectively); however, the risk of hypokalemia was significantly reduced with the addition of prednisone (p = 0.003). In comparison with prednisone alone, the addition of abiraterone did not increase the risk of hypertension (RR 1.22, 95% CI: 0.82 – 1.83, p=0.31), but significantly increased the risk of edema (RR 1.36, 95% CI: 1.10-1.69, p=0.004) and hypokalemia (RR 2.04, 95% CI: 1.42–2.92, p<0.001). Conclusions: There were differential effects of abiraterone on the development of hypertension, hypokalemia, and edema in patients with advanced prostate cancer. Further studies are recommended for optimal treatment.
Published Version
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