Low dose versus standard dose of corticosteroids in the management of adverse events of special interest from abiraterone acetate: data from a literature-based meta-analysis
- 465 Downloads
Abiraterone acetate is a CYP-17 inhibitor approved for the treatment of prostate cancer. Abiraterone acetate (AA) therapy is associated with toxicities, including hypokalemia, hypertension, liver function test abnormalities and cardiac events. These adverse events are traditionally managed with a standard dose of corticosteroids. However, preliminary data are available on the use of a lower dose of corticosteroids. The aim of this report is to perform a pooled analysis evaluating the risk ratio (RR) of AA-related adverse events of special interest associated with low or standard dose of corticosteroids. A total of 5374 cases from 4 randomized clinical trials were included. Subgroup analysis according to corticosteroids dosage revealed a higher RR of adverse events associated with a dose of 5 mg, compared to 10 mg. In particular, there was a statistically significant higher RR of hypokalemia and ALT/AST increase, and only a modest risk increase for cardiac disorders and hypertension. In conclusion, given the limitations of a literature-based study, in comparison with a meta-analysis based on individual patients’ data, our study identified a relatively small increase in RR for hypertension and cardiac disorders and a bigger increase of RR for hypokalemia and ALT/AST toxicity when 5 mg, rather than 10 mg of corticosteroids were administered to manage adverse events of special interest from AA. Further studies with specified end-points are awaited to confirm these results.
KeywordsAbiraterone Corticosteroids Safety Mineralocorticoid events
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
This article does not contain any studies with human participants or animals performed by any of the authors.
- 12.Fizazi K, Scher HI, Molina A, Logothetis CJ, Chi KN, Jones RJ, Staffurth JN, North S, Vogelzang NJ, Saad F, Mainwaring P, Harland S, Goodman OB Jr, Sternberg CN, Li JH, Kheoh T, Haqq CM, de Bono JS, COU-AA-301 Investigators. Abiraterone acetate for treatment of metastatic castration-resistant prostate cancer: final overall survival analysis of the COU-AA-301 randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol. 2012; 13(10):983–92. Erratum in: Lancet Oncol. 2012; 13(11):e464. Lancet Oncol. 2014; 15(9):e365.Google Scholar
- 13.Ryan CJ, Smith MR, Fizazi K, Saad F, Mulders PF, Sternberg CN, Miller K, Logothetis CJ, Shore ND, Small EJ, Carles J, Flaig TW, Taplin ME, Higano CS, de Souza P, de Bono JS, Griffin TW, De Porre P, Yu MK, Park YC, Li J, Kheoh T, Naini V, Molina A, Rathkopf DE, COU-AA-302 Investigators. Abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naive men with metastatic castration-resistant prostate cancer (COU-AA-302): final overall survival analysis of a randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol. 2015;16(2):152–60.CrossRefPubMedGoogle Scholar
- 14.Roviello G, Sigala S, Sandhu S, Bonetta A, Cappelletti MR, Zanotti L, Bottini A, Sternberg CN, Fox SB, Generali D. Role of the novel generation of androgen receptor pathway targeted agents in the management of castration-resistant prostate cancer: a literature based meta-analysis of randomized trials. Eur J Cancer. 2016;6(61):111–21.CrossRefGoogle Scholar
- 15.Roviello G, Sigala S, Danesi R, Re MD, Bonetta A, Cappelletti MR, Zanotti L, Bottini A, Generali D. Incidence and relative risk of adverse events of special interest in patients with castration resistant prostate cancer treated with CYP-17 inhibitors: a meta-analysis of published trials. Crit Rev Oncol Hematol. 2016;101:12.CrossRefPubMedGoogle Scholar
- 16.Fizazi K, Chi KN, de Bono JS, Gomella LG, Miller K, Rathkopf DE, Ryan CJ, Scher HI, Shore ND, De Porre P, Londhe A, McGowan T, Pelhivanov N, Charnas R, Todd MB, Montgomery B. Low incidence of corticosteroid-associated adverse events on long-term exposure to low-dose prednisone given with abiraterone acetate to patients with metastatic castration-resistant prostate cancer. Eur Urol. 2016;70:438.CrossRefPubMedPubMedCentralGoogle Scholar