title: [Late phase II study of exemestane in postmenopausal patients with breast cancer resistant to anti-estrogenic agents].
abstract: A multi-center trial of exemestane 25 mg, an oral aromatase irreversible inactivator, was conducted to evaluate its efficacy and safety in 33 postmenopausal patients, and to investigate the pharmacokinetics/serum hormone levels in 16 postmenopausal patients, respectively, with breast cancer and anti-estrogen resistance. Exemestane 25 mg was given once daily for up to 48 weeks (maximum). The objective of this study was to confirm the reproducibility of the results shown in two studies in other countries with similar patients, to investigate the possibility of extrapolating the overseas data to Japanese. The response rate (CR + PR) was 24.2% (8.33%), which exceeded the minimum number (6 cases) required to evaluate efficacy. The response rate in this study was very similar to that observed in the two international open studies. Adverse events (subjective/objective symptoms), in which a causal relationship with exemestane administration could not be excluded, were observed in 26 cases (78.8%). Of these, hot flushes, increased sweating, fatigue, and insomnia occurred in more than 10% of patients, which was similar to that observed in the two international open studies. Abnormal laboratory results occurring in more than 10% of patients, in which a causal relationship with exemestane administration could not be excluded, were as follows: lymphocyte count decrease, alkaline phosphate increase, GOT increase, GPT increase, gamma-GTP increase, triglyceride increase, and inorganic phosphate increase, most of which were either grade 1 or 2. A remarkable decrease in serum hormone concentration was observed only for estrogen. The values of AUC0-infinity at day 1 and AUC0-24 h at day 29 (steady state) were similar, suggesting no accumulative effect of exemestane. These results demonstrate the anti-tumor effect and safety of exemestane in postmenopausal anti-estrogen resistant breast cancer patients. The reproducibility of the results of the two foreign studies was verified in Japanese patients, and it is concluded that the foreign trial data on exemestane can be extrapolated to Japanese.
authors.affiliation: Division of Internal Medicine, National Cancer Center Hospital.
authors.forename: Toru
authors.initials: T
authors.lastname: Watanabe
authors.forename: Muneaki
authors.initials: M
authors.lastname: Sano
authors.forename: Masakazu
authors.initials: M
authors.lastname: Toi
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Saeki
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kanda
authors.forename: Shigeto
authors.initials: S
authors.lastname: Miura
authors.forename: Hideo
authors.initials: H
authors.lastname: Inaji
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sono
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Saeki
authors.forename: Reiki
authors.initials: R
authors.lastname: Nishimura
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Fujita
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000730:Androstadienes / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D047072:Aromatase Inhibitors; D001943:Breast Neoplasms / Q000188:drug therapy*; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D004791:Enzyme Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004965:Estrogen Antagonists / Q000494:pharmacology; D004967:Estrogens / Q000097:blood; D005260:Female; D019584:Hot Flashes / Q000139:chemically induced; D006801:Humans; D006973:Hypertension / Q000139:chemically induced; D008875:Middle Aged; D017698:Postmenopause; D015203:Reproducibility of Results
chemical_list: D000730:Androstadienes; D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors; D004965:Estrogen Antagonists; D004967:Estrogens; C056516:exemestane