Radiation Oncology/Prostate/Hormones/Drugs

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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  - Abarelix (Plenaxis)- withdrawn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)