Radiation Oncology/Prostate/Hormones/Drugs

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Prostate: Main Page | Prostate Overview | Screening and Prevention | Workup | Natural History | External Beam RT | IMRT | Androgen Suppression Therapy | Brachytherapy | Protons | Prostatectomy | Adjuvant RT after Prostatectomy | Salvage RT | Chemotherapy | Localized prostate cancer | Node Positive | Advanced disease | Recurrence after RT | Cryotherapy | RTOG Prostate Trials | Randomized Evidence


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      • Abarelix (Plenaxis)- withdrawn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 hydoxylase 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)