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- Abarelix (Plenaxis)- withdrawn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)
- Gonadotropin-releasing hormone agonists
- 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
- By inhibiting CYP17
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)