title: New generation aromatase inhibitors--from the advanced to the adjuvant setting.
abstract: Aromatase inhibitors (AIs) are a class of compounds that inhibit the cytochrome P450 aromatase enzyme that mediates conversion of androgens to estrogen in the adrenal gland. AIs have been approved for second-line and, more recently, first-line treatment of advanced breast cancer in postmenopausal women. The most recent, third generation of AIs are the non-steroidal agents anastrozole ('Arimidex') and letrozole, and the steroidal compound exemestane. As second-line therapy, anastrozole demonstrated a significant survival advantage over megestrol acetate (26.7 months v.s. 22.5 months; p < 0.025). Exemestane also produced better survival than megestrol acetate, although these data were less mature. Letrozole 2.5 mg has not demonstrated a survival advantage versus megestrol acetate in the second-line setting. As first-line therapy, anastrozole has demonstrated significant superiority in response rates with respect to time to progression (TTP) (11.1 months v.s. 5.6 months; p = 0.005) and has also demonstrated significantly greater clinical benefit rates compared with tamoxifen (59.1% v.s. 45.6%; p = 0.0098). Letrozole has also demonstrated significantly longer TTP than tamoxifen in the first-line setting (9.5 months v.s. 6 months; p = 0.0001). Important differences between the pharmacological profiles of these agents have been noted, particularly with respect to their effects on glucocorticoid metabolism; data for individual agents should not be extrapolated from one to another, particularly in the adjuvant setting.
mesh_terms: D000077384:Anastrozole; D000730:Androstadienes / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D047072:Aromatase Inhibitors; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D017024:Chemotherapy, Adjuvant; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D000077289:Letrozole; D009570:Nitriles / Q000627:therapeutic use; D014230:Triazoles / Q000627:therapeutic use
chemical_list: D000730:Androstadienes; D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors; D009570:Nitriles; D014230:Triazoles; D000077384:Anastrozole; D000077289:Letrozole; C056516:exemestane