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 * Abarelix (Plenaxis)- withdrawn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)