Maximal androgen blockade for advanced prostate cancer

Best Pract Res Clin Endocrinol Metab. 2008 Apr;22(2):331-40. doi: 10.1016/j.beem.2008.01.004.


Maximal androgen blockade (MAB) refers to the combination of medical (gonadotrophin-releasing hormone agonist) or surgical castration with an anti-androgen for the treatment of advanced prostate cancer. A substantial body of basic research has improved our understanding of the interactions between the anti-androgens, the androgen receptor, and androgen response elements in the genome. Anti-androgens act by two primary mechanisms: inhibition of ligand (androgen) binding to the androgen receptor, and inhibition of androgen-independent activation of the receptor. The latter mechanism occurs via several pathways, including inhibiting nuclear co-activators, activating co-suppressors, and inhibiting transcription of a variety of androgen-regulated genes. It is more accurate to refer to these compounds as androgen-receptor antagonists, since they inhibit activation whether this is androgen-mediated or not. Within the class of non-steroidal anti-androgens, there is variation in the degree to which ligand-independent activation is inhibited. Over the last 25 years, approximately 30 clinical trials have addressed the benefit of MAB versus monotherapy. Most of these trials have evaluated flutamide or nilutamide. Several meta-analyses suggest a modest survival benefit of these drugs, amounting to an 8% mortality reduction at 5 years. Preclinical data and two randomized trials -- one historic and one current -- suggest that bicalutamide may be a more effective drug in this respect. This requires confirmation pending further maturity of the current trial, which is the only one directly comparing bicalutamide plus castration to castration alone. In prostate cancer patients at high risk for mortality (based on extent of disease or prostate-specific antigen kinetics), combination therapy with bicalutamide should be considered in preference to monotherapy.

Publication types

  • Evaluation Study
  • Review

MeSH terms

  • Androgen Antagonists / administration & dosage*
  • Androgen Antagonists / adverse effects
  • Androgen Antagonists / economics
  • Anilides / administration & dosage
  • Anilides / adverse effects
  • Antineoplastic Agents, Hormonal / administration & dosage
  • Antineoplastic Agents, Hormonal / adverse effects
  • Antineoplastic Agents, Hormonal / economics
  • Antineoplastic Combined Chemotherapy Protocols / economics
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Combined Modality Therapy / adverse effects
  • Disease Progression
  • Dose-Response Relationship, Drug
  • Humans
  • Male
  • Meta-Analysis as Topic
  • Neoplasm Staging
  • Neoplasms, Hormone-Dependent / drug therapy
  • Nitriles / administration & dosage
  • Nitriles / adverse effects
  • Orchiectomy / adverse effects
  • Orchiectomy / methods
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / mortality
  • Prostatic Neoplasms / pathology
  • Randomized Controlled Trials as Topic
  • Survival Analysis
  • Tosyl Compounds / administration & dosage
  • Tosyl Compounds / adverse effects
  • Withholding Treatment


  • Androgen Antagonists
  • Anilides
  • Antineoplastic Agents, Hormonal
  • Nitriles
  • Tosyl Compounds
  • bicalutamide