title: Phase III randomized trial of droloxifene and tamoxifen as first-line endocrine treatment of ER/PgR-positive advanced breast cancer.
abstract: OBJECTIVE
  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.
  
  
  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 I year were excluded. All patients gave written informed consent, were randomized to 40mg 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 < or =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.
authors.affiliation: The University of Texas, M.D. Anderson Cancer Center, Houston 77030, USA. abuzdar@mdanderson.org
authors.forename: A
authors.initials: A
authors.lastname: Buzdar
authors.forename: D
authors.initials: D
authors.lastname: Hayes
authors.forename: A
authors.initials: A
authors.lastname: El-Khoudary
authors.forename: S
authors.initials: S
authors.lastname: Yan
authors.forename: P
authors.initials: P
authors.lastname: Lønning
authors.forename: M
authors.initials: M
authors.lastname: Lichinitser
authors.forename: R
authors.initials: R
authors.lastname: Gopal
authors.forename: G
authors.initials: G
authors.lastname: Falkson
authors.forename: K
authors.initials: K
authors.lastname: Pritchard
authors.forename: A
authors.initials: A
authors.lastname: Lipton
authors.forename: K
authors.initials: K
authors.lastname: Wolter
authors.forename: A
authors.initials: A
authors.lastname: Lee
authors.forename: K
authors.initials: K
authors.lastname: Fly
authors.forename: R
authors.initials: R
authors.lastname: Chew
authors.forename: M
authors.initials: M
authors.lastname: Alderdice
authors.forename: K
authors.initials: K
authors.lastname: Burke
authors.forename: P
authors.initials: P
authors.lastname: Eisenber
mesh_terms: D000367:Age Factors; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D004965:Estrogen Antagonists / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008875:Middle Aged; D011446:Prospective Studies; D013629:Tamoxifen / Q000008:administration & dosage / Q000819:agonists / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D013810:Therapeutic Equivalency; D016896:Treatment Outcome
chemical_list: D018931:Antineoplastic Agents, Hormonal; D004965:Estrogen Antagonists; D013629:Tamoxifen; C038345:droloxifene