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| Title: Clinical use of aromatase inhibitors in the treatment of
breast cancers. |
| Title Abreviation: J Cell Biochem Suppl |
Date of Pub: 1993 |
| Author: Manni A; |
| Issue/Part/Supplement: -HEADING- |
Volume Issue: 17G |
Pagination: 242-6 |
| MESH Headings: Aminoglutethimide (*TU); Animal; Aromatase
(*AI); Breast Neoplasms (*DT); Fadrozole (*TU); Female; Human; Nitriles (*TU); Rats;
Triazoles (*TU); -RN-; |
| Journal Title Code: K8K |
Publication Type: JOURNAL ARTICLE |
| Date of Entry: 940721N |
Entry Month: 9409 |
| Country: UNITED STATES |
Index Priority: 2 |
| Language: Eng |
Unique Identifier: 94276620 |
| Unique Identifier: 94276620 |
ISSN: 0733-1959 |
| Abstract: Estrogens are the major hormones supporting the
growth of human breast cancer. Aromatization of androgen precursors in peripheral tissues,
including the breast cancer itself, is the major source of estrogens in
postmenopausal women. Therefore, inhibition of the aromatase enzyme offers an effective
means of inducing regression of hormone-responsive breast cancer. Aminoglutethimide,
the first and most widely tested aromatase inhibitor, suppresses estrogen
production to the level of adrenalectomy and exerts an anti-tumor action comparable
to other standard endocrine therapies such as tamoxifen. However, conventional doses of
the drug (1000 mg daily) cause moderate toxicity and inhibit other critical cytochrome
P-450 steroidogenic enzymes, thus requiring concomitant glucocorticoid administration. New
non-steroidal, competitive aromatase inhibitors with greater selectivity and less toxicity
are being developed. The second generation compound, fadrazole (CGS 16949), lowers estrogen
production to a degree similar to aminoglutethimide (50-80%), but at much lower
doses (approximately 2 mg daily) and is associated with minimal toxicity. Although not
totally specific, this drug is sufficiently selective not to require simultaneous cortisol
replacement. CGS 16949 has been shown to possess significant anti-tumor action in
pilot studies and is currently being tested in Phase III trials. Recently, a third
generation inhibitor, CGS 20267, has been found to have virtually complete selectivity for
the aromatase enzyme. Furthermore, this drug suppresses estrogen biosynthesis to a
greater extent (approximately 90%) than previously observed with other aromatase
inhibitors. Such enhanced activity may lead to a superior anti-tumor action, and
may extend the use of this drug to a variety of other conditions where optimal suppression
of estrogen biosynthesis is desired. |
| Abstract By: Author |
| Address: Milton S. Hershey Medical Center, Department of Medicine,
Pennsylvania State University, Hershey 17033. |
| Number of References: 15 |
| Last Revision Date: 940808 |
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