Linked Life Data

2149503

Source:http://linkedlifedata.com/resource/pubmed/id/2149503

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1991-3-27
pubmed:abstractText
In postmenopausal women with breast cancer, aromatase, which is the enzyme converting androstenedione to estrone and testosterone to estradiol, is the rate-limiting step in estrogen biosynthesis. The currently available aromatase inhibitor, aminoglutethimide, effectively blocks estrogen production and products tumor regression in patients previously treated with tamoxifen. This drug, however, produces frequent side effects and blocks steroidogenic steps other than the aromatase enzyme. Thus, newer aromatase inhibitors with greater potency and specificity are under intense study. More than 20 such compounds have recently been developed. In several clinical trials, 4-hydroxyandrostenedione, given parenterally, has been highly active and specific for aromatase inhibition in patients with breast cancer. In two large recent studies, one-third of heavily pretreated woman experienced objective tumor regression with this therapy. CGS 16949A, a newer agent, is also in Phase III clinical trials. This compound is an imidazole derivative with nearly 1000-fold greater potency than aminoglutethimide. An initial Phase I study compared the potency of 0.6-16 mg daily in 12 postmenopausal women and found maximal suppression of urinary and plasma estrogens with 2 mg daily. The degree of inhibition was similar to that induced by aminoglutethimide or by surgical adrenalectomy. No CNS, hematologic or biochemical toxicity was observed. A larger Phase II study in 54 patients confirmed this high degree of potency of CGS since a plateau effect was observed at the 1.8, 2 and 4 mg daily doses. The endocrine effects were not absolutely specific as a blunting of ACTH-stimulated but not basal aldosterone levels were observed. This and other emerging aromatase inhibitors offer promise as pharmacologic methods to inhibit estrogen production specifically and without side effects.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0960-0760
pubmed:author
pubmed:issnType
Print
pubmed:day
20
pubmed:volume
37
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1029-35
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
1990
pubmed:articleTitle
Recent progress in development of aromatase inhibitors.
pubmed:affiliation
Department of Medicine, Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center, Hershey, PA 17033.
pubmed:publicationType
Journal Article, Review