Biologic activity of tamoxifen at low doses in healthy women

被引:86
作者
Decensi, A
Bonanni, BD
Guerrieri-Gonzaga, A
Gandini, S
Robertson, C
Johansson, H
Travaglini, R
Sandri, MT
Tessadrelli, A
Farante, G
Salinaro, F
Bettega, D
Barreca, A
Boyle, P
Costa, A
Veronesi, U
机构
[1] Chemoprevention Unit, European Institute of Oncology, Milan
[2] Div. of Epidemiol. and Biostatistics, European Institute of Oncology, Milan
[3] Department of Laboratory Medicine, European Institute of Oncology, Milan
[4] Division of Breast Surgery, European Institute of Oncology, Milan
[5] Department of Endocrinology, University of Genoa
[6] Italian League Against Cancer, Milan
[7] Dept. of Obstetrics and Gynecology, University of Brescia
[8] Angelo Bianchi Bonomi Haemophilia T., Milan
[9] Chemoprevention Unit, European Institute of Oncology, 20141 Milan, via Ripamonti
基金
美国国家卫生研究院;
关键词
D O I
10.1093/jnci/90.19.1461
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: Results of a clinical trial recently completed in the United States indicate that administration of tamoxifen (20 mg/day) to women 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 biomarkers when the drug was given at doses lower than those currently in use. Methods: In two sequential experiments, 127 healthy hysterectomized women aged 35-70 years were randomly assigned to one of the following 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 tamoxifen at 10 mg/alternate days (n = 32) (second experiment). Baseline and 2-month measurements of the following parameters were compared: 1) total cholesterol (primary end point) and other surrogate markers of cardiovascular disease, e.g., low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, and lipoprotein(a); 2) blood cell count; 3) fibrinogen; 4) antithrombin III; 5) osteocalcin; and, 6) in a subgroup of 103 women, insulin-like growth factor-I (IGF-I), a possible surrogate marker for breast cancer. Resuits: After adjustment for the baseline values, there were reductions in circulating levels 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 showed 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 disease. This study was hypothesis generating, and larger studies are warranted to assess the efficacy of tamoxifen at low doses.
引用
收藏
页码:1461 / 1467
页数:7
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