title: A summary of second-line randomized studies of aromatase inhibitors.
abstract: The new generation of selective aromatase inhibitors (anastrozole, letrozole and exemestane) offer a significant efficacy and safety advantage over both older agents in this class (aminoglutethimide) and the progestins (megestrol acetate (MA)), as second-line treatment for postmenopausal women with advanced hormone-dependent breast cancer who have failed on tamoxifen therapy. Exemestane, a steroidal aromatase inhibitor, has been shown to have activity after failure with the non-steroidal aromatase inhibitors, anastrozole and letrozole, and could be used as third-line treatment. Although the newer aromatase inhibitors belong to the same class and appear, from indirect comparisons, to have similar efficacy compared with the older therapies, they have different pharmacokinetic and pharmacodynamic profiles, suggesting the potential for clinical differences. Compared with exemestane and letrozole, anastrozole shows greater selectivity for aromatase, as it lacks any evidence of an effect on adrenal steroidogenesis and has no androgenic effects. Therefore, it is clear that these agents should not be considered to be similar in all respects. In summary, the introduction of the aromatase inhibitors represents a significant step forward in the treatment of advanced breast cancer in postmenopausal women. Studies in the adjuvant setting will ultimately determine whether the differences in pharmacokinetics and phamacodynamics will be of clinical relevance.
authors.affiliation: Department of Breast Medical Oncology, M.D. Anderson Cancer Center, M.D. University of Texas, Box 424, 1515 Holcombe Blvd, Houston, TX 77030, USA. abuzdar@mdanderson.org
authors.forename: A U
authors.initials: AU
authors.lastname: Buzdar
mesh_terms: D000616:Aminoglutethimide / Q000627:therapeutic use; D000077384:Anastrozole; D000730:Androstadienes / Q000627:therapeutic use; D047072:Aromatase Inhibitors; D001943:Breast Neoplasms / Q000188:drug therapy*; D004361:Drug Tolerance; D004791:Enzyme Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D020847:Estrogen Receptor Modulators / Q000627:therapeutic use; D017316:Fadrozole / Q000627:therapeutic use; D005260:Female; D006801:Humans; D000077289:Letrozole; D019290:Megestrol Acetate / Q000627:therapeutic use; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy*; D009570:Nitriles / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D013629:Tamoxifen / Q000627:therapeutic use; D014230:Triazoles / Q000627:therapeutic use
chemical_list: D000730:Androstadienes; D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors; D020847:Estrogen Receptor Modulators; D009570:Nitriles; D014230:Triazoles; D013629:Tamoxifen; D000616:Aminoglutethimide; D000077384:Anastrozole; D000077289:Letrozole; D017316:Fadrozole; C056516:exemestane; D019290:Megestrol Acetate