A phase I trial of CGS 16949A. A new aromatase inhibitor.

Abstract	CGS 16949A is a new, nonsteroidal competitive inhibitor of the aromatase enzyme. In this Phase I trial, 16 heavily pretreated postmenopausal patients with metastatic breast cancer were treated with escalating doses of CGS 16949A from 0.6 to 16 mg total daily oral dose. No hematologic, biochemical, or significant clinical toxicity was encountered. Endocrinologic and pharmacologic data were available from 12 of these patients. Maximum inhibition of estrogen biosynthesis was observed at a dose of 2 mg CGS 16949A daily. At this dose, the inhibition of estrogen biosynthesis was equivalent to 1000 mg aminoglutethimide (AG). The fall in plasma and urinary estrogens without a concomitant drop in androgens confirmed the specific blockade of aromatase activity. At doses of 4 to 16 mg daily, CGS 16949A appeared to inhibit the C21-hydroxylase enzyme as well. The t1/2 of CGS 16949A in the circulation was 10.5 hours. Of 16 evaluable patients there were two partial responses and seven patients with stable disease.
Authors	A Lipton, H A Harvey, L M Demers, J R Hanagan, M T Mulagha, G M Kochak, S Fitzsimmons, S I Sanders, R J Santen
Journal	Cancer (Cancer) Vol. 65 Issue 6 Pg. 1279-85 (Mar 15 1990) ISSN: 0008-543X [Print] United States
PMID	2137721 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Androgens Antineoplastic Agents Aromatase Inhibitors Estrogens Imidazoles Nitriles Aromatase Fadrozole
Topics	Adult Aged Androgens (blood) Antineoplastic Agents (administration & dosage, adverse effects, therapeutic use) Aromatase (administration & dosage, adverse effects) Aromatase Inhibitors Breast Neoplasms (blood, drug therapy, pathology) Drug Administration Schedule Drug Evaluation Estrogens (blood) Fadrozole Female Humans Imidazoles (administration & dosage, adverse effects, therapeutic use) Lymphatic Metastasis Menopause (blood) Middle Aged Nitriles (administration & dosage, adverse effects, therapeutic use)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.

Realize the full power of the drug-disease research graph!