Effect of the potent aromatase inhibitor fadrozole hydrochloride (CGS 16949A) in postmenopausal women with breast carcinoma

BACKGROUND. Fadrozole hydrochloride (CGS 16949A) is a highly potent, nonste roidal aromatase inhibitor that significantly lowers estrogen levels hi pos tmenopausal women and can be effective therapy for patients with advanced h ormone-dependent breast carcinoma. Circulating estradiol, estrone, and estr one sulfate are reduced to undetectable levels within weeks of the initiati on of therapy. Before this study, it was not known whether this decrease in serum estrogen levels results in altered parameters associated with cardio vascular disease. The authors examined the levels of several critical blood parameters that are important to cardiovascular risk for heart disease and thromboembolic disorders in patients treated with fadrozole. METHODS. Cholesterol, triglyceride, low density lipoprotein (LDL), high den sity lipoprotein (HDL), very low density lipoprotein (VLDL), antithrombin I II, protein C, protein S, and fibrinogen were serially measured in 21 postm enopausal women with advanced breast carcinoma treated with various doses o f fadrozole (1.8 mg/day, n = 3; 2.0 mg/day, n = 13; 4.0 mg/day, n = 5) over 3-24 months (mean, 15.8 months). A repeated measure analysis of variance w as applied to each cardiovascular variable to assess changes in the respons e over time. Analyses were performed separately for each dose group and wer e also pooled over the dose groups. RESULTS, There was no statistically significant change over time in lipid p arameters, namely, total cholesterol (P = 0.57), triglyceride (P = 0.27), L DL (P = 0.99), HDL (P = 0.30), and VLDL (P = 0.43), over the 24 months of t herapy. There were also no significant changes in coagulation factors, name ly, antithrombin III (P = 0.41), protein C (P = 0.49), or protein S (P = 0. 31), over the 24 months. However, an increase in fibrinogen that occurred o ver time did reach statistical significance (P = 0.011). CONCLUSIONS. With the exception of acute phase reactant fibrinogen, this st udy did not identify an increase in parameters associated with cardiovascul ar disease in women treated with fadrozole, a patent aromatase inhibitor. C ancer 1999;85: 100-3. (C) 1999 American Cancer Society.