Dose-dependent hormonal effects of toremifene in postmenopausal breast cancer patients

Purpose: The purpose of the study was to compare hormonal effects of three toremifene doses, 20 mg (TOR20), 40 mg (TOR40) and 60 mg (TOR60) administered daily, in postmenopausal women with advanced breast cancer. Methods: The study was randomized and open label in three parallel groups. Biochemical variables were identified as the serum concentrations of follicle stimulating hormone (FSH), luteinizing hormone (LH) and sex hormone binding globulin (SHBG). The changes were compared with objective clinical responses and to progression-free time. Adverse reactions and liver function test (aspartate aminotransferase, ASAT) were assessed for safety. Results: A total of 260 patients were randomly grouped (90 to TOR20, 81 to TOR40 and 89 to TOR60), Of these patients 29, 29 and 22 completed at least 3 months of treatment and the results were analyzed for biochemical variables. All treatments had intrinsic estrogen agonist activity by decreasing of serum FSH and LH and by increasing of SHBG during the first 3 months (P < 0.01). Dose TOR20 showed slightly longer times to exert maximum estrogenic effects than did the two higher doses. No increases in liver function tests were seen in any of the groups. Objective response rates were 24.4, 39.5 and 33.6% (P = 0.01) and median times-to-progression were 206, 189 and 196 days in TOR20, TOR40 and TOR60, respectively (P = 0.913). Fewer responses were observed in the TOR20 group than in TOR40 (P = 0.05). Adverse events were reported in 19, 23 and 30 patients. in the treatment groups (P = 0.20). The most frequently reported events were hot flushes and nausea. These were mostly mild or moderate, and only 1.5% of treatments was discontinued due to toxicity. Conclusions: Toremifene doses of 40 and 60 mg daily were effective and safe treatments of breast cancer in postmenopausal women, and no differences in their biochemical or clinical effects were seen. Toremifene at 20 mg/day had similar but slightly less potent antiestrogenic and estrogenic effects than the two higher doses.