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Antiandrogen Therapies
What are the agents in the antiandrogen class?
• Abiraterone (Zytiga®) and enzalutamide (Xtandi®)
What malignancies are each antiandrogen FDA approved for?
FDA-Approved Uses of Antiandrogen Therapies
Agent |
FDA Approval |
Abiraterone |
Prostate cancer |
Enzalutamide |
Prostate cancer |
Abbreviation: FDA, U.S. Food and Drug Administration.
How do the antiandrogens work?
• Abiraterone: inhibits the 17 α-hydroxylase/C17,20-lyase enzyme required for androgen biosynthesis (expressed in testicular, adrenal, and prostate tumor tissues); inhibits formations of the testosterone precursors, dehydroepiandrosterone (DHEA) and androstenedione
– Due to the inhibition of steroid synthesis by abiraterone, this agent must be taken with prednisone (see the following text) in order to avoid mineralocorticoid excess (caused by a rise in adrenocorticotropic hormone [ACTH] via a positive feedback loop) and consequences of low cortisol
• Enzalutamide: a pure androgen receptor inhibitor which, unlike traditional antiandrogens (eg, bicalutamide, flutamide), does not exhibit agonistic properties upon binding to the androgen receptor. Enzalutamide binds to the androgen receptor with much higher affinity than traditional antiandrogens, prevents nuclear translocation of the androgen receptor, and prevents androgen receptor association with DNA
What are the common dose ranges for each antiandrogen?
• Abiraterone: 1,000 mg orally daily (empty stomach) with prednisone 5 mg orally (PO) BID
• Enzalutamide: 160 mg orally once daily (with or without food)
Are the antiandrogens metabolized/eliminated renally or hepatically?
• Both agents are metabolized hepatically
• Enzalutamide is also renally eliminated (primarily as inactive metabolites)
Are there drug interactions with any of the antiandrogens?
• Abiraterone: CYP3A4 inhibitors/inducers; spironolactone (activates the androgen receptor); abiraterone inhibits CYP2C8/2C19/2C9/2D6/3A4
• Enzalutamide: a CYP2C8 and 3A4 substrate—reduce dose (80 mg) with strong CYP2C8 inhibitors; enzalutamide is an inducer of CYP3A4, CYP2C9, and CYP2C19
What are the adverse effects of each agent?
• Abiraterone: fluid retention/edema, hypokalemia, hypertension, cardiac disorders (ischemic heart disease, myocardial infarction, arrhythmias, heart failure), hepatotoxicity, hot flushes
• Enzalutamide: asthenia/fatigue is the most common side effect; arthralgia, hot flushes, hypertension, seizures are rare
What is the emetogenicity level of the antiandrogens?
• These agents are not chemotherapy and therefore are not in the National Comprehensive Cancer Network (NCCN) categorization; emetogenicity is minimal to low