title: Three dose regimens of fulvestrant in postmenopausal Japanese women with advanced breast cancer: results from a double-blind, phase II comparative study (FINDER1).
abstract: BACKGROUND
  FINDER1 compared efficacy, tolerability and pharmacokinetics (PK) of three fulvestrant dose regimens in postmenopausal Japanese women with estrogen receptor (ER)-positive locally advanced/metastatic breast cancer recurring or progressing after prior endocrine therapy.
  
  
  METHODS
  The primary end point of this randomised, multicentre, phase II study was objective response rate (ORR) and the secondary end points included time to progression (TTP), clinical benefit rate (CBR), PK profiles and tolerability. Postmenopausal women with ER-positive advanced breast cancer were randomised to 28-day cycles of fulvestrant approved dose (AD), loading dose (LD) or high dose (HD) until disease progression.
  
  
  RESULTS
  Hundred and forty-three patients (median age 61 years) received fulvestrant AD (n = 45), LD (n = 51) or HD (n = 47). ORR was similar across dose regimens: 11.1%, 17.6% and 10.6% for AD, LD and HD, respectively, with overlapping confidence intervals. TTP and CBR were also similar between groups (median TTP: 6.0, 7.5 and 6.0 months, respectively; CBR: 42.2%, 54.9% and 46.8% for AD, LD and HD, respectively). C(max) and area under the plasma concentration-time curve were dose proportional and PK steady state was reached earlier with LD and HD than with AD. All three doses were well tolerated, with a similar adverse-event profile and no emerging safety concerns.
  
  
  CONCLUSIONS
  Fulvestrant AD, LD and HD had similar efficacy and tolerability profiles in postmenopausal Japanese women with ER-positive advanced breast cancer.
authors.affiliation: Division of Breast Oncology, National Kyushu Cancer Center, Fukuoka. Electronic address: sohno@nk-cc.go.jp.
authors.forename: S
authors.initials: S
authors.lastname: Ohno
authors.affiliation: Department of Breast Surgery, Sagara Hospital, Kagoshima.
authors.forename: Y
authors.initials: Y
authors.lastname: Rai
authors.affiliation: Department of Breast Oncology, Aichi Cancer Center Hospital, Nagoya.
authors.forename: H
authors.initials: H
authors.lastname: Iwata
authors.affiliation: Department of Breast Surgery, Chiba Cancer Center, Chiba.
authors.forename: N
authors.initials: N
authors.lastname: Yamamoto
authors.affiliation: Department of Breast Surgery, Seirei Hamamatsu General Hospital, Shizuoka.
authors.forename: M
authors.initials: M
authors.lastname: Yoshida
authors.affiliation: Department of Breast and Endocrine Surgery, Kumamoto University Hospital, Kumamoto.
authors.forename: H
authors.initials: H
authors.lastname: Iwase
authors.affiliation: Department of Surgery, National Hospital Organization Osaka National Hospital, Osaka.
authors.forename: N
authors.initials: N
authors.lastname: Masuda
authors.affiliation: Department of Breast Surgical Oncology, St Luke's International Hospital, Tokyo.
authors.forename: S
authors.initials: S
authors.lastname: Nakamura
authors.affiliation: Department of Surgery, The Japanese Red Cross Nagasaki Atomic Bomb Hospital, Nagasaki.
authors.forename: H
authors.initials: H
authors.lastname: Taniguchi
authors.affiliation: Department of Surgery, Sakai Municipal Hospital, Osaka.
authors.forename: S
authors.initials: S
authors.lastname: Kamigaki
authors.affiliation: Department of Oncology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Noguchi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D044466:Asian People; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004958:Estradiol / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005260:Female; D000077267:Fulvestrant; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause / Q000187:drug effects / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D018931:Antineoplastic Agents, Hormonal; D000077267:Fulvestrant; D004958:Estradiol