title: Endocrine and clinical effects of exemestane (PNU 155971), a novel steroidal aromatase inhibitor, in postmenopausal breast cancer patients: a phase I study.
abstract: Clinical and endocrinological effects of exemestane (6-methylenandrosta-1,4-diene-3,17-dione; PNU 155971) were evaluated in an open Phase I study. Thirteen postmenopausal women suffering from advanced breast cancer received exemestane in escalating doses over a 12-week period. Starting on 5 mg once daily (o.d.), exemestane was subsequently escalated at 2-week intervals to 10, 25, 50, 100, and 200 mg o.d. Each patient subsequently continued treatment on the highest tolerated dose until time of progression. One patient terminated treatment after 6 days due to diarrhea that was probably not related to drug therapy, although a relationship could not be excluded. Apart from this, no serious side effects were seen during the dose escalation period. Exemestane (10 mg o.d.) caused maximal suppression of plasma estradiol (E2) and estrone (E1) to a mean of 14.6 and 5.8% of pretreatment levels, respectively, whereas 25 mg of exemestane o.d. suppressed estrone sulfate (E1S) to 8.9% of pretreatment levels. No fall in adrenal steroid levels was recorded. Exemestane (5 mg o.d.) suppressed urinary E2 and E1 to a mean of 11.9 and 12.2% of pretreatment levels, respectively. Administering exemestane at doses of 50-200 mg o.d. caused no further suppression of urinary E1, whereas urinary E2 fell to 6-7% of pretreatment levels. Median time to progression was 63 weeks. We conclude that exemestane is a well-tolerated aromatase inhibitor that effectively suppresses plasma and urinary estrogens in postmenopausal patients with breast cancer.
authors.affiliation: Department of Oncology, Haukeland University Hospital, N-5021 Bergen, Norway.
authors.forename: D C
authors.initials: DC
authors.lastname: Johannessen
authors.forename: T
authors.initials: T
authors.lastname: Engan
authors.forename: E
authors.initials: E
authors.lastname: Di Salle
authors.forename: M G
authors.initials: MG
authors.lastname: Zurlo
authors.forename: J
authors.initials: J
authors.lastname: Paolini
authors.forename: G
authors.initials: G
authors.lastname: Ornati
authors.forename: G
authors.initials: G
authors.lastname: Piscitelli
authors.forename: S
authors.initials: S
authors.lastname: Kvinnsland
authors.forename: P E
authors.initials: PE
authors.lastname: Lonning
mesh_terms: D000368:Aged; D000527:Alprostadil / Q000652:urine; D000728:Androgens / Q000097:blood; D000730:Androstadienes / Q000009:adverse effects*; D000970:Antineoplastic Agents / Q000009:adverse effects*; D047072:Aromatase Inhibitors; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000652:urine; D015232:Dinoprostone / Q000652:urine; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004958:Estradiol / Q000097:blood; D004970:Estrone / Q000031:analogs & derivatives / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017698:Postmenopause
chemical_list: D000728:Androgens; D000730:Androstadienes; D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; D004970:Estrone; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D000527:Alprostadil; D015232:Dinoprostone; C056516:exemestane; C017296:estrone sulfate