Phase III randomized trial of droloxifene and tamoxifen as first-line endocrine treatment of ER/PgR-positive advanced breast cancer

被引:58
作者
Buzdar, A
Hayes, D
El-Khoudary, A
Yan, S
Lonning, P
Lichinitser, M
Gopal, R
Falkson, G
Pritchard, K
Lipton, A
Wolter, K
Lee, A
Fly, K
Chew, R
Alderdice, M
Burke, K
Eisenberg, P
机构
[1] Univ Texas, MD Anderson Canc Ctr, Dept Breast Med Oncol, Houston, TX 77030 USA
[2] Georgetown Univ, Med Ctr, Washington, DC 20007 USA
[3] Cairo Univ, Natl Canc Inst, Cairo, Egypt
[4] Chinese Acad Med Sci, Canc Hosp, Beijing 100037, Peoples R China
[5] Haukeland Hosp, Bergen, Norway
[6] Ctr Canc Res, Moscow, Russia
[7] Tata Mem Hosp, Bombay 400012, Maharashtra, India
[8] Univ Pretoria, ZA-0002 Pretoria, South Africa
[9] Pretoria Acad Hosp, Pretoria, South Africa
[10] Toronto Sunnybrook Reg Canc Ctr, Toronto, ON, Canada
[11] MS Hershey Med Ctr, Hershey, PA USA
[12] Pfizer Inc, Pfizer Cent Res, Groton, CT 06340 USA
[13] Klinge Pharma GmbH, Munich, Germany
[14] Sutter CHS Canc Res Grp, Greenbrae, CA USA
关键词
advanced breast cancer; droloxifene; positive hormone receptors; randomized trial; tamoxifen;
D O I
10.1023/A:1015229630260
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose: This trial was designed to demonstrate equivalence between droloxifene 40 mg/d and tamoxifen 20 mg/d as first-line treatment in pre- and post-menopausal women with ER+ and/or PgR+ advanced breast cancer based on time to disease progression and tumor response. Materials and methods: One thousand three hundred fifty four women with measurable disease, previously untreated by hormonal or chemotherapy for advanced or recurrent breast cancer, were enrolled by 179 institutions in 35 countries. Patients were stratified at baseline for menopausal status. Patients receiving adjuvant hormonal therapy within 1 year were excluded. All patients gave written informed consent, were randomized to 40 mg droloxifene or 20 mg tamoxifen daily as single-agent therapy and underwent tumor assessment every 3 months. A central committee reviewed digitized images for all cases of tumor progression or objective response. Results: The hazard ratio (droloxifene/tamoxifen) for the primary endpoint, time to disease progression, was 1.287 favoring tamoxifen (95% C.I.: 1.114-1.487; p < .001). The objective response rate (CR + PR) was 22.4% for droloxifene and 28.6% for tamoxifen (p = .02). Tamoxifen was superior to droloxifene overall, among both pre- and postmenopausal patients and among patients <= 65 years; there was no difference among women >= 65 years. The hazard ratio for all-cause mortality was 0.871 (95% C.I.: 0.672-1.129; p = .29), favoring droloxifene but not statistically significant. Conclusions: Droloxifene was significantly less effective than tamoxifen overall and particularly among women under 65 years. Tamoxifen and droloxifene were both less effective in pre-menopausal women with receptor-positive disease compared to post-menopausal women. Further clinical development of droloxifene was stopped.
引用
收藏
页码:161 / 175
页数:15
相关论文
共 21 条
  • [1] ABE O, 1991, AM J CLIN ONCOL-CANC, V14, pS40
  • [2] BELLMUNT J, 1991, AM J CLIN ONCOL-CANC, V14, pS36
  • [4] PHASE-I TRIAL OF DROLOXIFENE IN PATIENTS WITH METASTATIC BREAST-CANCER
    BUZDAR, AU
    KAU, S
    HORTOBAGYI, GN
    THERIAULT, RL
    BOOSER, D
    HOLMES, FA
    WALTERS, R
    KRAKOFF, IH
    [J]. CANCER CHEMOTHERAPY AND PHARMACOLOGY, 1994, 33 (04) : 313 - 316
  • [5] CHEVALLIER B, 1993, B CANCER, V80, P624
  • [6] DESCHENES L, 1991, AM J CLIN ONCOL-CANC, V14, pS52
  • [7] INFLUENCE OF TREATMENT WITH THE ANTIESTROGEN 3-HYDROXYTAMOXIFEN (DROLOXIFENE) ON PLASMA SEX-HORMONE LEVELS IN POSTMENOPAUSAL PATIENTS WITH BREAST-CANCER
    GEISLER, J
    HAARSTAD, H
    GUNDERSEN, S
    RAABE, N
    KVINNSLAND, S
    LONNING, PE
    [J]. JOURNAL OF ENDOCRINOLOGY, 1995, 146 (02) : 359 - 363
  • [8] INFLUENCE OF DROLOXIFENE (3-HYDROXYTAMOXIFEN), 40 MG DAILY, ON PLASMA GONADOTROPINS, SEX-HORMONE BINDING GLOBULIN AND ESTROGEN-LEVELS IN POSTMENOPAUSAL BREAST-CANCER PATIENTS
    GEISLER, J
    EKSE, D
    HOSCH, S
    LONNING, PE
    [J]. JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, 1995, 55 (02) : 193 - 195
  • [9] DROLOXIFENE - A NEW ANTIESTROGEN - A PHASE-II STUDY IN ADVANCED BREAST-CANCER
    HAARSTAD, H
    GUNDERSEN, S
    WIST, E
    RAABE, N
    MELLA, O
    KVINNSLAND, S
    [J]. ACTA ONCOLOGICA, 1992, 31 (04) : 425 - 428
  • [10] Influence of droloxifene on metastatic breast cancer as first-line endocrine treatment
    Haarstad, H
    Lonning, PE
    Gundersen, S
    Wist, E
    Raabe, N
    Kvinnsland, S
    [J]. ACTA ONCOLOGICA, 1998, 37 (04) : 365 - 368