What are cyproterone and flutamide?

Cyproterone and Flutamide: Antiandrogen Medications for Prostate Cancer and Other Conditions

Cyproterone acetate and flutamide are antiandrogen medications that work by blocking the effects of androgens (male hormones) at their receptor sites, though they differ in their chemical structure, mechanism of action, and availability worldwide. 1

Types of Antiandrogens

Steroidal Antiandrogens: Cyproterone Acetate

• Mechanism of action:

  • Steroidal antiandrogen with progestational properties 1
  • Creates feedback inhibition of pituitary LHRH release to suppress testosterone production
  • Has direct effects on the androgen receptor 1
  • Available in Canada and Europe, but not in the United States 1

• Clinical uses:

  • Treatment of prostate cancer
  • Management of hirsutism in women 2, 3

• Benefits:

  • Reduces tumor flare when initiating LHRH agonist therapy 1
  • Fewer cardiovascular side effects compared to diethylstilbestrol (DES) 1
  • Effective for hirsutism treatment in women 2, 3

• Side effects:

  • Liver toxicity with long-term use 1, 4
  • Edema, weight gain, and shortness of breath (rare) 1
  • Diarrhea and elevated liver enzymes 1

Nonsteroidal Antiandrogens (NSAA): Flutamide

• Mechanism of action:

  • Competitively inhibits androgen binding to receptors in target tissue 1, 5
  • Blocks cellular binding of androgens without reducing testosterone levels 6
  • With therapy, a rise in serum testosterone is observed 1

• Clinical uses:

  • Treatment of prostate cancer (in combination with LHRH agonist) 1, 7
  • Management of hirsutism in women 2, 3

• Pharmacokinetics:

  • Rapidly and completely absorbed after oral administration 7
  • Extensively metabolized with a half-life of 5-6 hours 1, 7
  • Requires dosing three times a day 1
  • 94-96% bound to plasma proteins 7

• Benefits:

  • Oral medication with reversible side effects once therapy ceases 1
  • Equivalent overall survival compared to orchiectomy 1
  • Patients show greater improvements in sexual interest and physical capacity compared to castration 1
  • Effective for hirsutism treatment in women 2, 3

• Side effects:

  • Hepatotoxicity (liver injury) - can be severe and potentially fatal 1, 7, 4
  • Gynecomastia and breast pain (up to 39% of patients) 1
  • Higher withdrawal rate due to adverse events (9.8%) compared to other NSAAs 1

Clinical Applications

Prostate Cancer Treatment

• In prostate cancer, both medications are used to block the effects of androgens that stimulate cancer growth 1

• Combined androgen blockade (CAB) using an NSAA like flutamide with castration therapy shows:

  • Statistically significant improvement in overall survival compared to castration alone 1
  • HR: 0.88,95% CI, 0.82 to 0.95, P = 0.0009 1
  • Benefit appears after 5 years of follow-up 1

• In resource-constrained settings, combined androgen blockade using ADT plus a first-generation antiandrogen like flutamide may be offered for locally advanced nonmetastatic prostate cancer 1

Monitoring and Safety Considerations

• For flutamide, regular liver function tests are essential 7:

  • Before starting treatment
  • Monthly for the first 4 months
  • Periodically thereafter

• Warning signs of liver problems requiring immediate medical attention 7:

  • Loss of appetite, nausea, vomiting
  • Abdominal pain, fatigue
  • Flu-like symptoms
  • Brown urine or jaundice

Important Clinical Considerations

• Suspected cross-hepatotoxicity between flutamide and cyproterone acetate has been reported, suggesting caution when switching between these medications after hepatotoxicity 4
• In hirsutism treatment, flutamide may provide greater reduction in hirsutism scores compared to cyproterone acetate, though both are effective 3
• Flutamide is used in combination with an LHRH agonist for "total androgen blockade" in prostate cancer treatment 7

Comparative Efficacy

• For prostate cancer, combined androgen blockade with nonsteroidal antiandrogens (like flutamide) shows better outcomes than with steroidal antiandrogens (like cyproterone) 1
• For hirsutism in women, studies suggest flutamide may be slightly more effective than cyproterone acetate, though both provide significant improvement 2, 3