BIOLOGIC ACTIVITY OF TAMOXIFEN AT LOW-DOSES IN HEALTHY WOMEN

Citation
A. Decensi et al., BIOLOGIC ACTIVITY OF TAMOXIFEN AT LOW-DOSES IN HEALTHY WOMEN, Journal of the National Cancer Institute, 90(19), 1998, pp. 1461-1467
Citations number
59
Categorie Soggetti
Oncology
Volume
90
Issue
19
Year of publication
1998
Pages
1461 - 1467
Database
ISI
SICI code
Abstract
Background: Results of a clinical trial recently completed in the Unit ed States indicate that administration of tamoxifen (20 mg/day) to wom en at risk can reduce breast cancer incidence by approximately 50% but is associated with an increased risk of developing endometrial cancer and venous thromboembolic events. Since these adverse effects may be dose related, we investigated the effect of tamoxifen on several bioma rkers when the drug was given at doses lower than those currently in u se. Methods: In two sequential experiments, 127 healthy hysterectomize d women aged 35-70 years were randomly assigned to one of the followin g four treatment arms: placebo (n = 31) or tamoxifen at 20 mg/day (n = 30) (first experiment); or tamoxifen at 10 mg/day (n = 34) or tamoxif en at 10 mg/alternate days (n = 32) (second experiment). Baseline and 2-month measurements of the following parameters were compared: 1) tot al cholesterol (primary end point) and other surrogate markers of card iovascular disease, e.g., low-density lipoprotein cholesterol, high-de nsity lipoprotein cholesterol, triglycerides, and lipoprotein(a); 2) b lood cell count; 3) fibrinogen; 4) antithrombin III; 5) osteocalcin; a nd, 6) in a subgroup of 103 women, insulin-like growth factor-I (IGF-I ), a possible surrogate marker for breast cancer. Resuits: After adjus tment for the baseline values, there were reductions in circulating le vels of total cholesterol and IGF-I of the same magnitude in all three tamoxifen treatment arms. A similar pattern was observed for most of the other parameters. In the placebo arm, fibrinogen level, which show ed a decrease, was the only parameter exhibiting change, Conclusions: Up to a 75% reduction in the conventional dose of tamoxifen (i.e., 20 mg/day) does not affect the activity of the drug on a large number of biomarkers, most of which are surrogate markers of cardiovascular dise ase. This study was hypothesis generating, and larger studies are warr anted to assess the efficacy of tamoxifen at low doses.