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

Allan Lipton, Harold A. Harvey, Laurence M. Demers, John R. Hanagan, Mary T. Mulagha, Gregory M. Kochak, Sheila Fitzsimmons, Sherry I. Sanders, Richard J. Santen

Research output: Contribution to journalArticlepeer-review

76 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1279-1285
Number of pages7
JournalCancer
Volume65
Issue number6
DOIs
StatePublished - Mar 15 1990

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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