Radiation Oncology/Prostate/Hormones/Drugs

Classes of Androgen Suppressive Agents (Bilateral orchiectomy) Estrogens Diethyl stilbestrol (DES) Estramustine - derivative of estradiol with nitrogen mustard, an alkylating agent with estrogen-induced specificity Progestins Medroxyprogesterone acetate (Provera) Megestrol acetate (Megace) - synthetic progestin, able to lower testosterone and LH/FSH, and block binding of testosterone and dihydrotestosterone to androgen receptor Adrenal enzyme inhibitors Ketoconazole (works in the testis and adrenal glands) - weak antiandrogen, can reduce levels of androgens produced in testicles and adrenal glands Aminoglutethimide (first generation aromatase inhibitor) 5-Alpha reductase inhibitors - prevent conversion of testosterone into dihydrotestosterone (DHT) Finasteride (Proscar, Propecia) - inhibits only type II Dutasteride (Avodart) - inhibits both type I and II FCE 28260 (Experimental) Gonadotropin-releasing hormone inhibition (Injectable) Gonadotropin-releasing hormone agonists Leuprolide acetate (Lupron) Goserelin acetate (Zoladex) Gonadotropin-releasing hormone antagonists Abarelix (Plenaxis)- withdrawn Cetrorelix (Cetrotide) Degarelix (Firmagon) Ganirelix (Antagon) Non-steroidal anti-androgens (Oral) - androgen receptor blockers Flutamide (Eulexin) - 250 mg TID Nilutamide (Nilandron) Bicalutamide (Casodex) - 50 mg QD - appears to have least side effects Steroid anti-androgens - androgen receptor blockers Cyproterone acetate (Androcur) - also has weak progestational and glucocorticoid activity Abiraterone: Medication used in Castration Resistant Prostate Ca Increase OS 4m Inhibits biosynthesis of testosterione By inhibiting CYP17 A hydroxylase enzyme Produced in testis tumor adrenal Action Pregnolonone --> hydroxy-pregnolone Hydroxy-P --> DHEA Side effects: HTN Hypokalemia Fluid retention Required reduced dose in patients with liver disease Physiology Overview GnRH is released by hypothalamus in a pulsatile fashion, and acts on pituitary gland Anterior pituitary releases LH and FSH. LH acts on testes to produce testosterone Testosterone is metabolized to DHT by 5-alpha reductase DHT (and to much smaller extent testosterone) stimulate prostate cancer cells Side-effects Overview Hot flashes, effect on libido, muscle wasting, mood/personality changes, bone loss, gynecomastia (due to significantly increased levels of LH -> estrogen)