Three dose regimens of fulvestrant in postmenopausal Japanese women with advanced breast cancer: results from a double-blind, phase II comparative study (FINDER1).
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.
Ohno
S
S
Division of Breast Oncology, National Kyushu Cancer Center, Fukuoka. Electronic address: sohno@nk-cc.go.jp.
Rai
Y
Y
Department of Breast Surgery, Sagara Hospital, Kagoshima.
Iwata
H
H
Department of Breast Oncology, Aichi Cancer Center Hospital, Nagoya.
Yamamoto
N
N
Department of Breast Surgery, Chiba Cancer Center, Chiba.
Yoshida
M
M
Department of Breast Surgery, Seirei Hamamatsu General Hospital, Shizuoka.
Iwase
H
H
Department of Breast and Endocrine Surgery, Kumamoto University Hospital, Kumamoto.
Masuda
N
N
Department of Surgery, National Hospital Organization Osaka National Hospital, Osaka.
Nakamura
S
S
Department of Breast Surgical Oncology, St Luke's International Hospital, Tokyo.
Taniguchi
H
H
Department of Surgery, The Japanese Red Cross Nagasaki Atomic Bomb Hospital, Nagasaki.
Kamigaki
S
S
Department of Surgery, Sakai Municipal Hospital, Osaka.
Noguchi
S
S
Department of Oncology, Osaka University Graduate School of Medicine, Osaka, Japan.
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
D018931:Antineoplastic Agents, Hormonal; D000077267:Fulvestrant; D004958:Estradiol