THE EFFICACY OF CGS-20267 IN SUPPRESSING ESTROGEN BIOSYNTHESIS IN PATIENTS WITH ADVANCED STAGE BREAST-CANCER

The pharmacologic inhibition of aromatase activity has been the focus of clinical trials in patients with advanced stage breast cancer. Rece nt developments with imidazole compounds that inhibit aromatase activi ty suggest their clinical use as potent inhibitors of estrogen biosynt hesis in postmenopausal breast cancer patients. In this Phase I, open- label, dose-range finding study, we examined the inhibitory potency of CGS 20267 on blood and urine levels of estradiol, estrone and estrone sulfate in 8 patients with metastatic breast cancer. Studies included evaluation of adrenal and thyroid function to look for evidence of ge neral hydroxylase inhibition at dose levels effective for aromatase bl ockade. Patients were administered CGS 20267 at doses of 0.1 and 015 m g, once a day in ascending doses over a 12-week period. Preliminary da ta reveal that CGS 20267 elicits a striking suppression in plasma estr adiol, estrone and estrone sulphate which was observed in some patient s as quickly as within 24 h of the first dose. Estrogen suppression of over 90% was achieved within 2 weeks of therapy. No alterations in ei ther baseline or ACTH (cortrosyn) stimulated cortisol and aldosterone levels were observed through the 12 weeks of therapy. In addition, 24 h urine sodium and potassium values were not appreciably altered durin g therapy. We conclude that CGS 20267 is a potent, specific inhibitor of estrogen biosynthesis in postmenopausal patients with metastatic br east cancer and effectively reduces blood and urine estrogens to undet ectable levels.