Abstract
BackgroundHypertension is one of the major side effects associated with abiraterone in the treatment of advanced prostate cancer. The specific contribution of abiraterone to hypertension has not been defined. We performed a systematic review and meta-analysis of randomized clinical trials to determine its overall risk.MethodsDatabases including Pubmed (up to July 2018) and Google scholar (up to July 2018) were searched to identify relevant studies. Eligible studies were prospective randomized clinical trials with prostate cancer treated with abiraterone and prednisone. The incidence and relative risk (RR) of hypertension was calculated using random-effects or fixed-effects model depending on the heterogeneity of included studies.ResultsA total of five studies including 5445 patients were selected for analysis. Among patients receiving abiraterone, the overall incidences of all grade and high grade (grade 3 and 4) were 21.9% (95% CI: 13.6–33.2%) and 10.2% % (95% CI: 6.9–11.6%). Abiraterone was associated with a significantly increased risk of hypertension of all grade with a relative risk of 1.80 (95% CI: 1.47–2.19%, p < 0.001) and high grade with a relative risk of 2.11 (95%CI: 1.66–2.68%, p < 0.001) in comparison with controls. The risk of hypertension may be affected by concurrent use of prednisone with 5 mg daily is associated with higher incidence than that of prednisone 5 mg twice daily (32.4% vs 16.5%).ConclusionThere is a significant increase of developing hypertension in prostate cancer patients treated with abiraterone. Appropriate monitoring and management is strongly recommended to reduce the risk of cardiovascular events and treatment interruptions.
Highlights
Abiraterone acetate, the prodrug of abiraterone, is a selective inhibitor of androgen biosynthesis that potently blocks cytochrome P450 c17 (CYP17), a critical enzyme in testosterone synthesis, thereby blocking androgen synthesis by the adrenal glands and testes, as well as within the prostate tumor [1,2,3,4]
Search results Our search yielded a total of 35 articles on the clinical trials of abiraterone in prostate cancer from the literature
We have demonstrated a high incidence of all-grade hypertension (21.9, 95% CI: 13.6–33.2%) and high-grade hypertension (10.2, 95% CI: 6.9–11.5%) associated with abiraterone and prednisone
Summary
Abiraterone acetate, the prodrug of abiraterone, is a selective inhibitor of androgen biosynthesis that potently blocks cytochrome P450 c17 (CYP17), a critical enzyme in testosterone synthesis, thereby blocking androgen synthesis by the adrenal glands and testes, as well as within the prostate tumor [1,2,3,4]. The use of abiraterone in combination with prednisone has been shown to be effective in treating advanced prostate cancer and prolonging overall survival of these patients [5,6,7,8]. Mineralcorticoid excess such as hypokalemia, hypertension and fluid overload is a major side effect observed in clinical trials [6, 9]. The concurrent use of prednisone is recommended to mitigate adverse events related to the mineralocorticoid excess. Hypertension is consistently a major side effect observed in the clinical trials ranging even with the use of prednisone [10]. Hypertension is one of the major side effects associated with abiraterone in the treatment of advanced prostate cancer. We performed a systematic review and meta-analysis of randomized clinical trials to determine its overall risk
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