title: In vivo inhibition of aromatization by exemestane, a novel irreversible aromatase inhibitor, in postmenopausal breast cancer patients.
abstract: The effect of exemestane (6-methylenandrosta-1,4-diene-3,17-dione) 25 mg p.o. once daily on in vivo aromatization was studied in 10 postmenopausal women with advanced breast cancer. Aromatization was determined before treatment and after 6-8 weeks on therapy by administering a bolus injection of [3H]androstenedione (500 microCi) and [14C]estrone (5 microCi) followed by measurement of the isotope ratio of urinary estrogens after high-performance liquid chromatography purification. In addition, plasma endogenous estrogens were measured with highly sensitive radioimmunoassays after separation with high-performance liquid chromatography. Treatment with exemestane suppressed whole body aromatization from a mean pretreatment value of 2.059% to 0.042% (mean suppression of 97.9%). Plasma levels of estrone, estradiol, and estrone sulfate were found to be suppressed by 94.5%, 92.2%, and 93.2%, respectively. This is the first study revealing near total aromatase inhibition in vivo with the use of a steroidal aromatase inhibitor. The observation that exemestane is a highly potent aromatase inhibitor, together with the fact that the drug is administered p.o. and causes limited side effects, suggests that exemestane is a promising new drug for the treatment of hormone sensitive breast cancer.
authors.affiliation: Department of Oncology, Haukeland University Hospital, Bergen, Norway.
authors.forename: J
authors.initials: J
authors.lastname: Geisler
authors.forename: N
authors.initials: N
authors.lastname: King
authors.forename: G
authors.initials: G
authors.lastname: Anker
authors.forename: G
authors.initials: G
authors.lastname: Ornati
authors.forename: E
authors.initials: E
authors.lastname: Di Salle
authors.forename: P E
authors.initials: PE
authors.lastname: Lønning
authors.forename: M
authors.initials: M
authors.lastname: Dowsett
mesh_terms: D000284:Administration, Oral; D000730:Androstadienes / Q000627:therapeutic use*; D000735:Androstenedione / Q000378:metabolism; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001141:Aromatase / Q000378:metabolism; D047072:Aromatase Inhibitors; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology*; D002250:Carbon Radioisotopes; D004958:Estradiol / Q000097:blood / Q000378:metabolism; D004967:Estrogens / Q000097:blood / Q000652:urine; D004970:Estrone / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism; D005260:Female; D006801:Humans; D017698:Postmenopause; D014316:Tritium
chemical_list: D000730:Androstadienes; D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; D002250:Carbon Radioisotopes; D004967:Estrogens; D014316:Tritium; D004970:Estrone; D000735:Androstenedione; D004958:Estradiol; D001141:Aromatase; C056516:exemestane; C017296:estrone sulfate