Costa L A, Kopreski M S, Demers L M, Chinchilli V M, Santen R J, Harvey H A, Lipton A
Unidade de Oncologia, Hospital de Santa Maria, Lisbon, Portugal.
Cancer. 1999 Jan 1;85(1):100-3. doi: 10.1002/(sici)1097-0142(19990101)85:1<100::aid-cncr14>3.0.co;2-5.
Fadrozole hydrochloride (CGS 16949A) is a highly potent, nonsteroidal aromatase inhibitor that significantly lowers estrogen levels in postmenopausal women and can be effective therapy for patients with advanced hormone-dependent breast carcinoma. Circulating estradiol, estrone, and estrone sulfate are reduced to undetectable levels within weeks of the initiation of therapy. Before this study, it was not known whether this decrease in serum estrogen levels results in altered parameters associated with cardiovascular 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.
Cholesterol, triglyceride, low density lipoprotein (LDL), high density lipoprotein (HDL), very low density lipoprotein (VLDL), antithrombin III, protein C, protein S, and fibrinogen were serially measured in 21 postmenopausal women with advanced breast carcinoma treated with various doses of 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 was applied to each cardiovascular variable to assess changes in the response over time. Analyses were performed separately for each dose group and were also pooled over the dose groups.
There was no statistically significant change over time in lipid parameters, namely, total cholesterol (P=0.57), triglyceride (P=0.27), LDL (P=0.99), HDL (P=0.30), and VLDL (P=0.43), over the 24 months of therapy. There were also no significant changes in coagulation factors, namely, 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 over time did reach statistical significance (P=0.011).
With the exception of acute phase reactant fibrinogen, this study did not identify an increase in parameters associated with cardiovascular disease in women treated with fadrozole, a potent aromatase inhibitor.
