| Agent |
Dosing |
Mechanism |
Adverse Effects |
Clinical Pearls |
| Luteinizing hormone-releasing hormone agonists |
| Goserelin (Zoladex) |
3.6 mg SC every 4 wk 10.8 mg SC every 12 wk |
Initial increase in LH and FSH followed by down-regulation of pituitary receptors via negative feedback loop and decreased testosterone production |
Acute: Tumor flare, gynecomastia, hot flashes, bone pain, erectile dysfunction, edema, injection-site pain Long-term: Osteoporosis, obesity, decreased muscle mass, insulin resistance, dyslipidemia, risk of diabetes and CV events |
Considered equivalent in efficacy and safety Risk of tumor flare in first 1–2 wk; start antiandrogen at least 1 wk prior and continue for at least 1 wk Consider calcium and vitamin D supplementation and DEXA screening |
| (Lupron, Eligard) |
22.5 mg IM/SC every 3 mo 30 mg IM/SC every 4 mo 45 mg IM/SC every 6 mo |
| Triptorelin (Trelstar) |
3.75 mg IM every 4 wk 11.25 mg IM every 12 wk 22.5 mg IM every 24 wk |
| Histrelin (Vantas) |
50 mg SC implant every 12 mo |
| Luteinizing hormone-releasing hormone antagonist |
| Degarelix (Firmagon) |
240 mg SC (2 120-mg injections, then 80 mg SC every 28 days (starting 28 days after loading dose) |
Directly inhibits GnRH receptors in pituitary gland, resulting in rapid androgen deprivation |
Short-term and long-term side effects are similar to LHRH agonists LFT abnormalities |
|
| Antiandrogens |
| Bicalutamide (Casodex) |
50 mg PO daily |
Block androgens at the receptor site |
Hot flashes, edema, asthenia, gynecomastia, LFT abnormalities, diarrhea Flutamide causes more diarrhea Nilutamide may cause night blindness |
|
| Flutamide (Eulexin) |
250 mg PO TID |
| Nilutamide (Nilandron) |
300 mg PO TID x 30 days, then 150 mg daily |
| Pregnenolone analogue |
| Abiraterone (Zytiga) |
1,000 mg PO daily with prednisone 5 mg PO daily |
Prevents testosterone formation by irreversibly inhibiting CYP17, rate-limiting enzyme in androgen production |
Fluid retention, hypertension, hypokalemia, hypophosphatemia, atrial fibrillation, fatigue, hepatotoxicity, hot flashes, arthralgia, bone fractures |
Administer on empty stomach Concomitant prednisone administration reduces risk of adrenal insufficiency Major CYP3A4 substrate; increase abiraterone to 1,000 mg twice daily with concomitant strong CYP3A4 inducer Moderate CYP2D6 inhibitor |
| Receptor-signaling pathway inhibitor |
| Enzalutamide (Xtandi) |
160 mg PO daily |
Blocks androgen-receptor translocation, DNA binding, and recruitment of coactivator causing cellular apoptosis |
Fatigue, headache, diarrhea, hot flashes, back pain, arthralgia, hypertension, seizures (rare) In clinical trials, falls and fall injuries occurred more frequently in enzalutamide arm |
Major CYP2C8 and CYP3A4 substrate; reduce enzalutamide dose to 80 mg daily with concomitant CYP2C8 inhibitors and increase enzalutamide dose to 240 mg daily with concomitant CYP3A4 inducers Strong CYP3A4 and moderate CYP2C9 inducer |
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