title: The efficacy of CGS 20267 in suppressing estrogen biosynthesis in patients with advanced stage breast cancer.
abstract: The pharmacologic inhibition of aromatase activity has been the focus of clinical trials in patients with advanced stage breast cancer. Recent developments with imidazole compounds that inhibit aromatase activity suggest their clinical use as potent inhibitors of estrogen biosynthesis 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 general hydroxylase inhibition at dose levels effective for aromatase blockade. Patients were administered CGS 20267 at doses of 0.1 and 0.25 mg, once a day in ascending doses over a 12-week period. Preliminary data reveal that CGS 20267 elicits a striking suppression in plasma estradiol, estrone and estrone sulphate which was observed in some patients 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 either 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 during therapy. We conclude that CGS 20267 is a potent, specific inhibitor of estrogen biosynthesis in postmenopausal patients with metastatic breast cancer and effectively reduces blood and urine estrogens to undetectable levels.
authors: Department of Medicine, Pennsylvania State University, Milton S. Hershey Medical Center, Hershey 17033.
authors: L M
authors: LM
authors: Demers
authors: A
authors: A
authors: Lipton
authors: H A
authors: HA
authors: Harvey
authors: K B
authors: KB
authors: Kambic
authors: H
authors: H
authors: Grossberg
authors: C
authors: C
authors: Brady
authors: R J
authors: RJ
authors: Santen
mesh_terms: D000450:Aldosterone / Q000097:blood; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D047072:Aromatase Inhibitors; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D003366:Cosyntropin; D004958:Estradiol / Q000097:blood / Q000652:urine; D004967:Estrogens / Q000378:metabolism*; D004970:Estrone / Q000031:analogs & derivatives / Q000097:blood / Q000652:urine; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D000077289:Letrozole; D009367:Neoplasm Staging; D009570:Nitriles / Q000627:therapeutic use / Q000633:toxicity*; D011188:Potassium / Q000652:urine; D012964:Sodium / Q000652:urine; D013997:Time Factors; D014230:Triazoles / Q000627:therapeutic use / Q000633:toxicity*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D047072:Aromatase Inhibitors; D004967:Estrogens; D009570:Nitriles; D014230:Triazoles; D003366:Cosyntropin; D004970:Estrone; D000450:Aldosterone; D004958:Estradiol; D000077289:Letrozole; D012964:Sodium; C017296:estrone sulfate; D011188:Potassium; D006854:Hydrocortisone