World Library  
Flag as Inappropriate
Email this Article

Exemestane

Article Id: WHEBN0003173222
Reproduction Date:

Title: Exemestane  
Author: World Heritage Encyclopedia
Language: English
Subject: Medroxyprogesterone acetate, Cyproterone acetate, Everolimus, Pfizer, Testolactone
Collection: Aromatase Inhibitors, Enantiopure Drugs, Pfizer
Publisher: World Heritage Encyclopedia
Publication
Date:
 

Exemestane

Exemestane
Systematic (IUPAC) name
6-Methylideneandrosta-1,4-diene-3,17-dione[1]
Clinical data
Trade names Aromasin
AHFS/Drugs.com
MedlinePlus
Pregnancy
category
  • D
Legal status
  • (Prescription only)
Routes of
administration
Oral
Pharmacokinetic data
Bioavailability ~60%
Protein binding 90%
Biological half-life 24 hours
Identifiers
CAS Registry Number  Y
ATC code L02
PubChem CID:
IUPHAR/BPS
DrugBank  Y
ChemSpider  Y
UNII  Y
KEGG  Y
ChEBI  N
ChEMBL  Y
Chemical data
Formula C20H24O2
Molecular mass 296.403 g/mol
 N   

Exemestane, FCE-24304, (trade name Aromasin) is a drug used to treat breast cancer. It is a member of the class of drugs known as aromatase inhibitors. Some breast cancers require estrogen to grow. Those cancers have estrogen receptors (ERs), and are called ER-positive. They may also be called estrogen-responsive, hormonally-responsive, or hormone-receptor-positive. Aromatase is an enzyme that synthesizes estrogen. Aromatase inhibitors block the synthesis of estrogen. This lowers the estrogen level, and slows the growth of cancers.

Contents

  • Function 1
  • Clinical uses 2
  • Therapeutic Efficacy 3
  • See also 4
  • References 5
  • External links 6

Function

Exemestane is an oral steroidal aromatase inhibitor that is used in ER-positive breast cancer in addition to surgery and/or radiation in post-menopausal women.

The main source of estrogen is the ovaries in premenopausal women, while in post-menopausal women most of the body's estrogen is produced via the conversion of androgens into estrogen by the aromatase enzyme in the peripheral tissues (i.e. adipose tissue like that of the breast) and a number of sites in the brain. Estrogen is produced locally via the actions of the aromatase enzyme in these peripheral tissues where it acts locally. Any circulating estrogen in post-menopausal women as well as men is the result of estrogen escaping local metabolism and entering the circulatory system.[2]

Exemestane is an irreversible, steroidal aromatase inactivator, structurally related to the natural substrate androstenedione. It acts as a false substrate for the aromatase enzyme, and is processed to an intermediate that binds irreversibly to the active site of the enzyme causing its inactivation, an effect also known as "suicide inhibition." By being structurally similar to enzyme targets, Exemestane permanently binds to the enzymes, preventing them from converting androgen into estrogen.

The estrogen suppression rate for exemestane varies from 35% for estradiol (E2) to 70% for estrone (E1).[3]

Clinical uses

Exemestane is indicated for the adjuvant treatment of postmenopausal women with estrogen-receptor positive early breast cancer who have received two to three years of tamoxifen and are switched to it for completion of a total of five consecutive years of adjuvant hormonal therapy.[4] US FDA approval was in October 2005.[5]

Exemestane is indicated for the treatment of advanced breast cancer in postmenopausal women whose disease has progressed following tamoxifen therapy.[6]

A Phase III trial has been reported which concluded that the use of exemestane in postmenopausal women at an increased risk for breast cancer reduced the incidence of invasive breast cancer. In 4,560 women, after 35 months, the administration of exemestane at a dose of 25 mg/day resulted in a 65% reduction in the risk of breast cancer compared with placebo; annual incidence rates were 0.19% and 0.55%, respectively (hazard ratio: 0.35; 95% CI [0.18-0.70]; p = 0.002).[7]

Therapeutic Efficacy

Oral exemestane 25 mg/day for 2–3 years of adjuvant therapy was generally more effective than 5 years of continuous adjuvant tamoxifen in the treatment of postmenopausal women with early-stage estrogen receptor-positive/unknown receptor status breast in a large well-designed trial. Preliminary data from the open-label TEAM trial comparing exemestane with tamoxifen indicates that exemestane 25 mg/day is also effective in the primary adjuvant treatment of early-stage breast cancer in postmenopausal women.[8]

Interim phase III trial results in 2011 show that adding Afinitor (everolimus) to exemestane therapy against advanced breast cancer can significantly improve progression-free survival compared with exemestane therapy alone.[9]

See also

References

  1. ^ Exemestane, at ChEBI
  2. ^ Simpson ER (2003). "Sources of estrogen and their importance". The Journal of Steroid Biochemistry and Molecular Biology 86 (3–5): 225–30.  
  3. ^ NELLY MAURAS, JOHN LIMA, DEVAL PATEL, ANNIE RINI, ENRICO DI SALLE, AMBROSE KWOK, AND BARBARA LIPPE. "Pharmacokinetics and Dose Finding of a Potent Aromatase Inhibitor, Aromasin (Exemestane), in Young Males". The Journal of Clinical Endocrinology & Metabolism. 2003 http://jcem.endojournals.org/content/88/12/5951.full.pdf. 
  4. ^ Coombes RC; et al. (2007). "Survival and safety of exemestane versus tamoxifen after 2–3 years' tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial".  
  5. ^ http://www.cancer.gov/cancertopics/druginfo/fda-exemestane
  6. ^ Aromasin For Advanced Breast Cancer
  7. ^ Goss, Paul E. (June 6, 2011). "Exemestane Offers New Option for Breast Cancer Prevention". American Society of Clinical Oncology. Retrieved June 6, 2011. 
  8. ^ Deeks ED, Scott LJ. (2009). "Exemestane: A Review of its Use in Postmenopausal Women with Breast Cancer". Drugs 2009:69(7):889–918.  
  9. ^ "Positive Trial Data Leads Novartis to Plan Breast Cancer Filing for Afinitor by Year End". 2011. 

External links

  • Aromasin official website
  • Aromasin prescribing information


This article was sourced from Creative Commons Attribution-ShareAlike License; additional terms may apply. World Heritage Encyclopedia content is assembled from numerous content providers, Open Access Publishing, and in compliance with The Fair Access to Science and Technology Research Act (FASTR), Wikimedia Foundation, Inc., Public Library of Science, The Encyclopedia of Life, Open Book Publishers (OBP), PubMed, U.S. National Library of Medicine, National Center for Biotechnology Information, U.S. National Library of Medicine, National Institutes of Health (NIH), U.S. Department of Health & Human Services, and USA.gov, which sources content from all federal, state, local, tribal, and territorial government publication portals (.gov, .mil, .edu). Funding for USA.gov and content contributors is made possible from the U.S. Congress, E-Government Act of 2002.
 
Crowd sourced content that is contributed to World Heritage Encyclopedia is peer reviewed and edited by our editorial staff to ensure quality scholarly research articles.
 
By using this site, you agree to the Terms of Use and Privacy Policy. World Heritage Encyclopedia™ is a registered trademark of the World Public Library Association, a non-profit organization.
 


Copyright © World Library Foundation. All rights reserved. eBooks from Project Gutenberg are sponsored by the World Library Foundation,
a 501c(4) Member's Support Non-Profit Organization, and is NOT affiliated with any governmental agency or department.