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Activity and Safety of the Antiestrogen EM-800, the Orally Active Precursor of Acolbifene, in Tamoxifen-Resistant Breast Cancer

From the Laval University Medical Research Center and Centre Hospitalier Universitaire de Québec; Hôpital du Saint-Sacrement; Hôpital Laval, Québec City; McGill University; Hôpital Sacré-Coeur; Centre Hospitalier Universitaire de Montréal (CHUM); Hôpital Charles-Lemoyne, Montreal; Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Québec, Canada

Address reprint requests to Fernand Labrie, MD, Oncology and Molecular Endocrinology Research Center, Laval University Medical Center, 2705 Laurier Blvd, T-3-67, Quebec City, Quebec, G1V 4G2, Canada; E-mail: fernand.labrie{at}crchul.ulaval.ca

PURPOSE: To determine the efficacy and safety of EM-800 (SCH-57050), the precursor of acolbifene, a new, highly potent, orally active, pure antiestrogen in the mammary gland and endometrium, for the treatment of tamoxifen-resistant breast cancer.

PATIENTS AND METHODS: Forty-three post menopausal/ovariectomized women with breast cancer who had received tamoxifen, either for metastatic disease or as adjuvant to surgery for 1 year, and had relapsed were treated in a prospective, multicenter, phase II study with EM-800 (20 mg/d [n = 21] or 40 mg/d [n = 22] orally).

RESULTS: Thirty-seven patients had estrogen receptor (ER)-positive tumors (>10 fmol/mg; mean, 146 fmol/mg cytosolic protein), three patients had ER-negative/progesterone receptor-positive tumors, and three patients had undetermined ER status. The objective response rate to EM-800 was 12%, with one complete response and four partial responses. Ten patients (23%) had stable disease for 3 months, and 7 patients (16%) had stable disease for 6 months. With a median follow-up of 29 months, median duration of response was 8 months (range, 7 to 71+ months). Treatment with EM-800 was well tolerated. No significant adverse events related to the study drug were observed clinically or biochemically.

CONCLUSION: EM-800 produced responses in a significant proportion of patients with tamoxifen-resistant breast cancer, thus showing that this highly potent, selective estrogen receptor modulator, which lacks estrogenic activity in the mammary gland and endometrium, has incomplete cross-resistance with tamoxifen, thus suggesting additional benefits in the treatment of breast cancer.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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