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

A. Buzdar, D. Hayes, A. El-Khoudary, S. Yan, P. Lønning, M. Lichinitser, R. Gopal, G. Falkson, K. Pritchard, Allan Lipton, K. Wolter, A. Lee, K. Fly, R. Chew, M. Alderdice, K. Burke, P. Eisenberg

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)161-175
Number of pages15
JournalBreast Cancer Research and Treatment
Volume73
Issue number2
DOIs
StatePublished - Jun 3 2002

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Tamoxifen
Breast Neoplasms
Therapeutics
Disease Progression
droloxifene
Neoplasms
Informed Consent
Drug Therapy
Mortality

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Buzdar, A. ; Hayes, D. ; El-Khoudary, A. ; Yan, S. ; Lønning, P. ; Lichinitser, M. ; Gopal, R. ; Falkson, G. ; Pritchard, K. ; Lipton, Allan ; Wolter, K. ; Lee, A. ; Fly, K. ; Chew, R. ; Alderdice, M. ; Burke, K. ; Eisenberg, P. / Phase III randomized trial of droloxifene and tamoxifen as first-line endocrine treatment of ER/PgR-positive advanced breast cancer. In: Breast Cancer Research and Treatment. 2002 ; Vol. 73, No. 2. pp. 161-175.
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abstract = "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.",
author = "A. Buzdar and D. Hayes and A. El-Khoudary and S. Yan and P. L{\o}nning and M. Lichinitser and R. Gopal and G. Falkson and K. Pritchard and Allan Lipton and K. Wolter and A. Lee and K. Fly and R. Chew and M. Alderdice and K. Burke and P. Eisenberg",
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Buzdar, A, Hayes, D, El-Khoudary, A, Yan, S, Lønning, 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 2002, 'Phase III randomized trial of droloxifene and tamoxifen as first-line endocrine treatment of ER/PgR-positive advanced breast cancer', Breast Cancer Research and Treatment, vol. 73, no. 2, pp. 161-175. https://doi.org/10.1023/A:1015229630260

Phase III randomized trial of droloxifene and tamoxifen as first-line endocrine treatment of ER/PgR-positive advanced breast cancer. / Buzdar, A.; Hayes, D.; El-Khoudary, A.; Yan, S.; Lønning, P.; Lichinitser, M.; Gopal, R.; Falkson, G.; Pritchard, K.; Lipton, Allan; Wolter, K.; Lee, A.; Fly, K.; Chew, R.; Alderdice, M.; Burke, K.; Eisenberg, P.

In: Breast Cancer Research and Treatment, Vol. 73, No. 2, 03.06.2002, p. 161-175.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Phase III randomized trial of droloxifene and tamoxifen as first-line endocrine treatment of ER/PgR-positive advanced breast cancer

AU - Buzdar, A.

AU - Hayes, D.

AU - El-Khoudary, A.

AU - Yan, S.

AU - Lønning, P.

AU - Lichinitser, M.

AU - Gopal, R.

AU - Falkson, G.

AU - Pritchard, K.

AU - Lipton, Allan

AU - Wolter, K.

AU - Lee, A.

AU - Fly, K.

AU - Chew, R.

AU - Alderdice, M.

AU - Burke, K.

AU - Eisenberg, P.

PY - 2002/6/3

Y1 - 2002/6/3

N2 - 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.

AB - 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.

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U2 - 10.1023/A:1015229630260

DO - 10.1023/A:1015229630260

M3 - Article

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JF - Breast Cancer Research and Treatment

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