New aromatase inhibitors for the treatment of advanced breast cancer in postmenopausal women.
Inhibition of the enzyme aromatase, the rate limiting step in estrogen production, is an effective endocrine treatment of advanced postmenopausal breast cancer. Recently, several new aromatase inhibitors have been developed to improve efficacy and reduce toxicity compared to the prototype aromatase inhibitor aminoglutethimide. Aromatase inhibitors can be divided into two types. The first are the non-steroidal inhibitors that have a mechanism of action similar to aminoglutethimide. The second are the steroidal inhibitors that function as a false substrate for aromatase. Of the non-steroidal aromatase inhibitors, two drugs, anastrozole and letrozole, have recently been registered for the second line endocrine treatment of advanced postmenopausal breast cancer after failure on tamoxifen. The phase III studies of these drugs indicate at least equal efficacy compared to current second line treatment with aminoglutethimide or megestrol acetate. Their toxicity profile, however, is much more favourable. This makes them the drugs of choice for the second line endocrine treatment of advanced breast cancer in postmenopausal patients, who failed during adjuvant or first line treatment with tamoxifen. Of the steroidal aromatase inhibitors, the orally active drug exemestane is still in phase III clinical study; the registration is expected in 1999.
de Jong
P C
PC
Department of Internal Medicine, St. Antonius Hospital, Nieuwegein, The Netherlands.
Blijham
G H
GH
D000616:Aminoglutethimide / Q000494:pharmacology / Q000627:therapeutic use*; D000077384:Anastrozole; D000730:Androstadienes / Q000627:therapeutic use; D000735:Androstenedione / Q000031:analogs & derivatives / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D047072:Aromatase Inhibitors; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D017024:Chemotherapy, Adjuvant / Q000639:trends; D017326:Clinical Trials, Phase III as Topic; D005260:Female; D006801:Humans; D000077289:Letrozole; D019290:Megestrol Acetate / Q000627:therapeutic use; D009570:Nitriles / Q000627:therapeutic use; D017698:Postmenopause; D014230:Triazoles / Q000627:therapeutic use
D000730:Androstadienes; D000970:Antineoplastic Agents; D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D009570:Nitriles; D014230:Triazoles; D000616:Aminoglutethimide; C060523:vorozole; D000077384:Anastrozole; D000735:Androstenedione; D000077289:Letrozole; C056516:exemestane; C014594:formestane; D019290:Megestrol Acetate