Theoretical considerations for the ideal aromatase inhibitor.
A definition of the theoretical components of an ideal aromatase inhibitor is developed, one aspect of which is completeness of enzyme inhibition. The three triazole inhibitors, letrozole, vorozole and anastrozole all inhibit whole body aromatisation by > 96% at their clinically used doses and vorozole and letrozole were more effective in Phase III clinical trials than aminoglutethimide (250 mg bd) which achieves < 90% inhibition. The possibility is considered that the apparent small differences between the triazoles may be associated with differences in clinical effectiveness. These new compounds merit consideration for studies of breast cancer prevention.
Dowsett
M
M
Royal Marsden Hospital, London, UK. mitch@icr.ac.uk
D000616:Aminoglutethimide / Q000627:therapeutic use; D000077384:Anastrozole; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000627:therapeutic use*; D047072:Aromatase Inhibitors; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000517:prevention & control*; D017326:Clinical Trials, Phase III as Topic; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D000077289:Letrozole; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000517:prevention & control*; D009570:Nitriles / Q000627:therapeutic use; D014230:Triazoles / Q000627:therapeutic use
D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors; D009570:Nitriles; D014230:Triazoles; D000616:Aminoglutethimide; C060523:vorozole; D000077384:Anastrozole; D000077289:Letrozole