Activity and safety of the antiestrogen EM-800, the orally active precursor of acolbifene, in tamoxifen-resistant breast cancer.

Abstract

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 > or = 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 > or = 3 months, and 7 patients (16%) had stable disease for > or = 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: Fernand Labrie, Pierre Champagne, Claude Labrie, Jean Roy, Jacques Laverdière, Louise Provencher, Martin Potvin, Yvan Drolet, Michael Pollak, Lawrence Panasci, Bernard L'Espérance, Jean Dufresne, Jean Latreille, Jean Robert, Benoît Samson, Jacques Jolivet, Louise Yelle, Lionel Cusan, Pierre Diamond, Bernard Candas
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 22 Issue 5 Pg. 864-71 (Mar 01 2004) ISSN: 0732-183X [Print] United States
• PMID: 14990642 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Journal Article, Multicenter Study)

Chemical References

• Benzopyrans
• Estrogen Antagonists
• Prodrugs
• Propionates
• Tamoxifen
• EM 800

Topics

• Administration, Oral
• Adult
• Aged
• Aged, 80 and over
• Benzopyrans (administration & dosage, pharmacokinetics)
• Biological Availability
• Breast Neoplasms (drug therapy, mortality, pathology)
• Carcinoma (drug therapy, secondary)
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Drug Resistance, Neoplasm
• Estrogen Antagonists (administration & dosage, pharmacokinetics)
• Female
• Humans
• Lymphatic Metastasis
• Maximum Tolerated Dose
• Middle Aged
• Neoplasm Staging
• Prodrugs
• Propionates (administration & dosage, pharmacokinetics)
• Prospective Studies
• Risk Assessment
• Survival Analysis
• Tamoxifen (administration & dosage)
• Treatment Outcome