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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The growth inhibitory effect of a new non-steroidal aromatase inhibitor, CGS16949A (Fadrozole hydrochloride: [4-(5,6,7,8-tetrahydro-imidazo-[1,5a]-pyridin-5-yl) benzonitrile monohydro chloride]) was studied in human breast cancer cells MCF-7 and T47D. The aromatase activity of MCF-7 was inhibited by CGS16949A in a dose-dependent manner (IC50: 2.8 x 10(-9) M). The cells were incubated for 120 h in phenol red free RPMI 1640 containing 5% stripped foetal calf serum, 10(-8) M testosterone and various concentrations of CGS16949A. Testosterone-induced MCF-7 growth was inhibited by CGS16949A almost completely at the concentrations as low as 10(-9) M, but was not inhibited by antiandrogenic cyproterone acetate (6-chloro-1 beta,2 beta-dihydro-17-hydroxy-3'-H- cyclopropa[1,2]-pregna-1,4,6-triene-3,20-dione acetate: CPA). On the other hand, the growth of T47D stimulated by testosterone was not inhibited by CGS16949A, but was inhibited by CPA. These data suggested that the aromatization of androgens should participate in the growth of MCF-7 and that one of the growth inhibitory mechanisms of CGS16949A should be the inhibition of the intracellular aromatase activity.
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PMID:Anti-tumour effect of aromatase inhibitor, CGS16949A, on human breast cancer cells. 762 94

Fadrozole hydrochloride is a potent aromatase inhibitor with proven clinical effectiveness. However, its optimal dose and its effects on serum aldosterone levels/electrolyte balance have been disputed. To resolve these issues, a double-blind randomised endocrine study of three doses of fadrozole hydrochloride [0.5 mg twice daily (bd); 1.0 mg bd; 2.0 mg bd] was conducted in 80 (68 evaluable) postmenopausal patients with advanced breast cancer over a period of 3 months. There were substantial falls in the serum levels of oestradiol, oestrone and oestrone sulphate. For oestrone only, there was a significant effect of dose (on-treatment means: 0.5 mg, 38.0 pmol/l; 1.0 mg, 25.0 pmol/l; 2.0 mg, 23.9 pmol/l). All oestrogens showed a similar pattern in relation to time, with the 3-month mean being higher than those at 1 and 2 months, and this was significant for oestradiol (P = 0.012). There was an indication that complete suppression of oestradiol and oestrone was not maintained throughout the 12-h dosing period, but the data and its interpretation are complicated by a minor diurnal rhythm in these parameters. There were significant increases in 17-hydroxyprogesterone and androstenedione which may be due to a block of 11 beta-hydroxylase. There was a statistically non-significant fall in aldosterone levels (P = 0.06) during treatment (median pretreatment, 446 pmol/l; median decrease, 125 pmol/l). However, the concurrent significant fall in the plasma sodium: potassium ratio indicated that changes in aldosterone secretion did occur. None of these effects on adrenal pathways was of a degree which is likely to have clinically relevant consequences. It is concluded that fadrozole hydrochloride achieves near maximal suppression of oestrogens at 1 mg bd, and that its effects on aldosterone synthesis are unlikely to be of clinical significance.
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PMID:Endocrine changes with the aromatase inhibitor fadrozole hydrochloride in breast cancer. 783 1

Fadrozole hydrochloride at a dose of 2 mg b.i.d. has been shown to be an effective aromatase inhibitor in advanced stage breast cancer patients as determined by its ability to significantly suppress endogenous estrogen biosynthesis over a 12-week period. Continued suppression of circulating estrogen levels over a prolonged period has not yet been examined in published reports. In this study, we report the extended use of fadrozole hydrochloride at a maintenance dose of 2 mg b.i.d. in a cohort of 11 patients extending to 973 days of therapy. Results show that the degree of suppression of plasma and urinary estrogens was maintained in all patients throughout the extended period of drug use. Continued estradiol suppression of over 50% or greater from baseline was observed, as was continued suppression of estrone to over 80% from baseline. Cortisol determinations after 9 months of treatment showed no suppression from baseline. The aldosterone values and responses to cortrosyn stimulation continued to be suppressed as first noted following the initial 3 months of the core clinical trial. Objective tumor response noted in the core clinical trial did not change until disease progression. These findings suggest that fadrozole hydrochloride maintains its ability to suppress the aromatase enzyme during long term use. No observable escape from suppression of plasma and urinary estrogens occurred during prolonged treatment.
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PMID:The effects of long term fadrozole hydrochloride treatment in patients with advanced stage breast cancer. 838 41