title: A randomized trial of megestrol acetate with or without premarin in the treatment of potentially responsive metastatic breast cancer. A Study of the Eastern Cooperative Oncology Group (E2185).
abstract: BACKGROUND
  Human breast cancer cells in vitro exhibit increased levels of progestin receptors (PgR) after brief exposure to physiologic concentrations of estrogens. Prior clinical studies have positively correlated the responsiveness of metastatic breast cancer to progestin therapy with the level of PgR in the tumor cells.
  
  
  METHODS
  These observations were used as the scientific basis for a randomized clinical trial by the Eastern Cooperative Oncology Group (ECOG) to compare the effectiveness of megestrol acetate (MEG) alone in a daily dose of 160 mg with MEG alternated with premarin in a dose of 1.25 mg/day on the first 3 days of a 14 day cycle (PRE/MEG). From 1985 through 1989, 266 eligible and fully evaluable patients were randomized to 1 of the treatment arms and accrued to this trial. All patients were postmenopausal with biochemical estrogen cytosol protein receptor (ER) positive (> or = 10 fm/mg) tumors. The treatment groups were balanced with respect to performance status, number of involved organ systems, and PgR levels.
  
  
  RESULTS
  Forty-five of 135 (33%) (95% confidence interval [CI], 25-42%) patients receiving MEG experienced a partial (PR) or complete (CR) response. Thirty-one of 131 (23%) (95% CI, 17-32%) patients receiving PRE/MEG achieved a PR or CR. Survival was not influenced by treatment selection. However, median time to progression was seven months for patients receiving MEG and four months for the group receiving PRE/MEG (P = 0.03). The treatment failure hazard rate was higher for patients with a short disease free interval after primary treatment of the breast cancer, poor performance status, non-white race, and visceral disease. Survival was negatively impacted by short disease free interval, administration of prior radiation therapy, prior treatment for metastatic disease, and hepatic involvement.
  
  
  CONCLUSIONS
  Sequential treatment with premarin and megestrol acetate is not superior to treatment with megace alone in potentially hormone responsive patients with advanced breast cancer.
authors.affiliation: Flower Hospital, Sylvania, Ohio 43560, USA.
authors.forename: C D
authors.initials: CD
authors.lastname: Cobau
authors.forename: K
authors.initials: K
authors.lastname: Declercq
authors.forename: D
authors.initials: D
authors.lastname: Neuberg
authors.forename: J N
authors.initials: JN
authors.lastname: Ingle
authors.forename: D C
authors.initials: DC
authors.lastname: Tormey
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008535:Megestrol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D019290:Megestrol Acetate; D009362:Neoplasm Metastasis; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy / Q000401:mortality; D015996:Survival Rate
chemical_list: D018931:Antineoplastic Agents, Hormonal; D004966:Estrogens, Conjugated (USP); D008535:Megestrol; D019290:Megestrol Acetate