Use of Prednisone With Abiraterone Acetate in Metastatic Castration-Resistant Prostate Cancer

被引:74
|
作者
Auchus, Richard J. [1 ]
Yu, Margaret K. [2 ]
Nguyen, Suzanne [3 ]
Mundle, Suneel D. [3 ,4 ]
机构
[1] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI 48109 USA
[2] Janssen Res & Dev, Los Angeles, CA USA
[3] Johnson & Johnson, Janssen Sci Affairs LLC, Horsham, PA USA
[4] Rush Univ, Med Ctr, Dept Biochem, Chicago, IL 60612 USA
来源
ONCOLOGIST | 2014年 / 19卷 / 12期
关键词
Adrenal cortex hormones; 17-(3-Pyridyl)-5,16-androstadien-3 beta-acetate; Steroid; 17-alpha-hydroxylase; Prednisone; Prostatic neoplasms; CONGENITAL ADRENAL-HYPERPLASIA; BONE-MINERAL DENSITY; 11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE-1; MITOXANTRONE PLUS PREDNISONE; LOW-DOSE DEXAMETHASONE; I CLINICAL-TRIAL; RHEUMATOID-ARTHRITIS; INFLUENZA VACCINATION; ANDROGEN RECEPTOR; CORTICOSTEROID-THERAPY;
D O I
10.1634/theoncologist.2014-0167
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Abiraterone acetate, a prodrug of the CYP17A1 inhibitor abiraterone that blocks androgen biosynthesis, is approved for treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) in combination with prednisone or prednisolone 5 mg twice daily. This review evaluates the basis for the effects of prednisone on mineral ocorticoid-related adverse events that arise because of CYP17A1 inhibition with abiraterone. Coadministration with the recommended dose of glucocorticoid compensates for abiraterone-induced reductions in serum cortisol and blocks the compensatory increase in adrenocorticotropic hormone seen with abiraterone. Consequently, 5 mg prednisone twice daily serves as a glucocorticoid replacement therapy when coadministered with abiraterone acetate, analogous to use of glucocorticoid replacement therapy for certain endocrine disorders. We searched PubMed to identify safety concerns regarding glucocorticoid use, placing a focus on longitudinal studies in autoimmune and inflammatory diseases and cancer. In general, glucocorticoid-related adverse events, including bone loss, immunosuppression, hyperglycemia, mood and cognitive alterations, and myopathy, appear dose related and tend to occur at doses and/or treatment durations greater than the low dose of glucocorticoid approved in combination with abiraterone acetate for the treatment of mCRPC. Although glucocorticoids are often used to manage tumor-related symptoms or to prevent treatment-related toxicity, available evidence suggests that prednisone and dexamethasone might also offer modest therapeutic benefit in mCRPC. Given recent improvements in survival achieved for mCRPC with novel agents in combination with prednisone, the risks of these recommended glucocorticoid doses must be balanced with the benefits shown for these regimens.
引用
收藏
页码:1231 / 1240
页数:10
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