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To determine the activity of combination hormonal therapy for platinum-resistant ovarian carcinoma, we treated 20 patients with leuprolide acetate 7.5 mg intramuscularly once a month and tamoxifen 20 mg orally twice a day. Among the 17 evaluable patients, two patients (12%; 95% CI: 0-27) had a partial response, each lasting 7 months. An additional five patients(29%; 95% CI: 8-51) experienced disease stabilization with a median duration of 5 months. This response rate is not significantly different from previously published studies using either leuprolide acetate or tamoxifen alone. The median survival duration was 14.4 months and this was not significantly different from that of our previous study with high-dose Taxol(P = 0.0668). The treatment was well-tolerated, with minimal toxicity. Combination hormone therapy with leuprolide acetate and tamoxifen does not result in increased activity compared with either drug used alone for platinum-refractory ovarian carcinoma. However, hormonal therapy should remain an important consideration for this disease since it has documented activity with minimal associated toxicity. [ABSTRACT FROM AUTHOR]

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.Results: 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. [ABSTRACT FROM AUTHOR]