title: [Early phase II dose-finding study of exemestane in postmenopausal patients with advanced/recurrent breast cancer].
abstract: Exemestane was administered orally to postmenopausal women with advanced/recurrent breast cancer at a dose of 10 mg/day or 25 mg/day once daily for more than 8 weeks in order to evaluate the drug's anti-tumor effects and safety in a dose-finding study. The response rate (CR + PR) in the 10 mg and 25 mg group was 25.0% (8/32) and 31.4% (11/35), respectively, demonstrating no significant differences between the two groups, yet a higher efficacy rate was observed in 25 mg group. The efficacy rate in hormone-treatment-resistant patients within the 10 mg and 25 mg groups was 14.3% (3/21) and 26.1% (6/23), respectively, demonstrating more than a 20% response rate in 25 mg group. Incidences of the adverse events of which relevance to the drug could not be excluded were 30.6% (11/36) in the 10 mg group. 13.9% (5/36) in the 25 mg group and 22.2% (16/72) in the total group. The major adverse events were, hot flashes, numbness of the limbs, nausea, headache etc. Abnormal findings in clinical laboratory tests were as follows: ALP increase; GOT increase; GPT increase; gamma-GTP increase; total cholesterol increase; urinary sediment present. Abnormal findings in endocrine function were as follows: aldosterone decrease; testosterone.cortisol.DHEA-S decrease. But discontinuation due to abnormal laboratory findings was not found. No abnormal findings in physical tests were observed. A significant decrease in plasma estrogen concentration at week 4 was observed in both the 10 mg and 25 mg groups compared with baseline. These low levels were maintained throughout the study period. On the basis of these results, the efficacy of exemestane 25 mg/day was verified to be slightly higher than 10 mg/day. In addition the safety profile had no major adverse events to notice. In these patients with advanced/recurrent breast cancer, 25 mg/day was recommended as the most appropriate dose to be used clinically.
authors.affiliation: Saitama Cancer Center.
authors.forename: Toshio
authors.initials: T
authors.lastname: Tabei
authors.forename: Masami
authors.initials: M
authors.lastname: Ogita
authors.forename: Kouichi
authors.initials: K
authors.lastname: Hirata
authors.forename: Susumu
authors.initials: S
authors.lastname: Satomi
authors.forename: Michio
authors.initials: M
authors.lastname: Kimura
authors.forename: Rikiya
authors.initials: R
authors.lastname: Abe
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Morishita
authors.forename: Morihiko
authors.initials: M
authors.lastname: Kimura
authors.forename: Jirou
authors.initials: J
authors.lastname: Andou
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Higashi
authors.forename: Keiichi
authors.initials: K
authors.lastname: Yoshino
authors.forename: Ken
authors.initials: K
authors.lastname: Tominaga
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Kajiwara
authors.forename: Masaki
authors.initials: M
authors.lastname: Kitajima
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Koyanagi
authors.forename: Toru
authors.initials: T
authors.lastname: Watanabe
authors.forename: Susumu
authors.initials: S
authors.lastname: Yamaguchi
authors.forename: Mamoru
authors.initials: M
authors.lastname: Watanabe
authors.forename: Kazushige
authors.initials: K
authors.lastname: Toyama
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kanda
authors.forename: Yoshitomo
authors.initials: Y
authors.lastname: Kashiki
authors.forename: Shigeto
authors.initials: S
authors.lastname: Miura
authors.forename: Zhunzo
authors.initials: Z
authors.lastname: Kobayashi
authors.forename: Hideaki
authors.initials: H
authors.lastname: Aoyama
authors.forename: Itsuo
authors.initials: I
authors.lastname: Miyazaki
authors.forename: Takahiro
authors.initials: T
authors.lastname: Oka
authors.forename: Hiroki
authors.initials: H
authors.lastname: Koyama
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kinoshita
authors.forename: Morito
authors.initials: M
authors.lastname: Monden
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Takai
authors.forename: Eiji
authors.initials: E
authors.lastname: Yayoi
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Takatsuka
authors.forename: Tatehiro
authors.initials: T
authors.lastname: Kajiwara
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sonoo
authors.forename: Tesuya
authors.initials: T
authors.lastname: Toge
authors.forename: Shigemitsu
authors.initials: S
authors.lastname: Takashima
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Nomura
authors.forename: Kazuharu
authors.initials: K
authors.lastname: Nagao
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Fujita
mesh_terms: D000284:Administration, Oral; D000730:Androstadienes / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D004334:Drug Administration Schedule; D004967:Estrogens / Q000097:blood; D005260:Female; D006261:Headache / Q000139:chemically induced; D019584:Hot Flashes / Q000139:chemically induced; D006801:Humans; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D017698:Postmenopause; D011960:Receptors, Estrogen / Q000032:analysis
chemical_list: D000730:Androstadienes; D000970:Antineoplastic Agents; D004967:Estrogens; D011960:Receptors, Estrogen; C056516:exemestane