Fulvestrant

Fulvestrant
Systematic (IUPAC) name
(7α,17β)-7-{9-[(4,4,5,5,5-pentafluoropentyl)sulfinyl]nonyl}estra-1,3,5(10)-triene-3,17-diol
Clinical data
Trade names Faslodex
AHFS/Drugs.com monograph
Pregnancy
category
  • D
Legal status
  • ℞ (Prescription only)
Routes of
administration		 Intramuscular injection
Pharmacokinetic data
Protein binding 99%
Biological half-life 40 days
Identifiers
CAS Number 129453-61-8 YesY
ATC code L02BA03
PubChem CID 104741
IUPHAR/BPS 1015
DrugBank DB00947 N
ChemSpider 94553 N
UNII 22X328QOC4 YesY
KEGG D01161 N
ChEBI CHEBI:31638
ChEMBL CHEMBL1358 N
Synonyms ICI-182,780
Chemical data
Formula C32H47F5O3S
Molar mass 606.772 g/mol
 NYesY (what is this?)  (verify)

Fulvestrant (trade name Faslodex, by AstraZeneca) is a drug treatment of hormone receptor-positive metastatic breast cancer in postmenopausal women with disease progression following anti-estrogen therapy. It is a complete estrogen receptor antagonist with no agonist effects, which in addition, accelerates the proteasomal degradation of the estrogen receptor.[1] The drug has poor oral bioavailability, and is administered monthly via intramuscular injection.[2]

Clinical uses

Fulvestrant is a selective estrogen receptor degrader (SERD).[3] It is indicated for the treatment of hormone receptor positive metastatic breast cancer in postmenopausal women with disease progression following anti-estrogen therapy. The dosing schedule for fulvestrant remains under investigation in an attempt to optimize its effectiveness.[4]

Clinical trials

Metastatic or locally advanced breast cancer

Fulvestrant provided effective second-line therapy in this setting for postmenopausal women who had relapsed or progressed after previous endocrine therapy.[5]

In particular 4 clinical trials in this setting did show similar efficacy to the other hormonal agents (aromatase inhibitors and tamoxifen) with good tolerability profile. Fulvestrant had a lower incidence of joint disorders.[6][7]

NICE evaluation

The U.K. National Institute for Health and Clinical Excellence (NICE) said in 2011 that it found no evidence Faslodex was significantly better than existing treatments, so its widespread use would not be a good use of resources for the country's National Health Service

The first month's treatment of Faslodex, which starts with a loading dose, costs £1,044.82 ($1,666), and subsequent treatments cost £522.41 a month.

A month's supply of anastrozole (Arimidex), which is off patent, costs 92 pence/day, and letrozole (Femara) costs £1.57/day- [8][9][10]

Patent extension

The original patent for Faslodex expired in October 2004. Drugs subject to pre-marketing regulatory review are eligible for patent extension, and for this reason AstraZeneca got an extension of the patent to December 2011.[11][12]

AstraZeneca has filed later patents. There is no generic Faslodex available.[13] A later patent for Faslodex expires in January 2021.[14]

See also

References

  1. ↑ Scott SM, Brown M, Come SE (2011). "Emerging data on the efficacy and safety of fulvestrant, a unique antiestrogen therapy for advanced breast cancer". Expert Opin Drug Saf 10 (5): 819–26. doi:10.1517/14740338.2011.595560. PMID 21699443.
  2. ↑ S. Eva Singletary; Geoffrey L. Robb; Gabriel N. Hortobagyi (1 January 2004). Advanced Therapy of Breast Disease. PMPH-USA. pp. 568–. ISBN 978-1-55009-262-2.
  3. ↑ Wardell SE, Marks JR, McDonnell DP. (2011). "The turnover of estrogen receptor α by the selective estrogen receptor degrader (SERD) fulvestrant is a saturable process that is not required for antagonist efficacy.". Biochem Pharmacol. 82 (2).
  4. ↑ Angela Mae Obermiller, PharmD; and Mehmet Sitki Copur, MD (2011). "The Longstanding Quest for a Better Endocrine Therapy Continues High-Dose Fulvestrant: Have We Found Its Effective Dose, Combination, Setting, or Sequence?". Contemporary Oncology 3 (1).
  5. ↑ Croxtall JD, McKeage K (2011). "Fulvestrant: a review of its use in the management of hormone receptor-positive metastatic breast cancer in postmenopausal women". Drugs 71 (3): 363–80. doi:10.2165/11204810-000000000-00000. PMID 21319872.
  6. ↑ Valachis A, Mauri D, Polyzos NP, Mavroudis D, Georgoulias V, Casazza G (2010). "Fulvestrant in the treatment of advanced breast cancer: a systematic review and meta-analysis of randomized controlled trials". Crit. Rev. Oncol. Hematol. 73 (3): 220–7. doi:10.1016/j.critrevonc.2009.03.006. PMID 19369092.
  7. ↑ Flemming J, Madarnas Y, Franek JA (2009). "Fulvestrant for systemic therapy of locally advanced or metastatic breast cancer in postmenopausal women: a systematic review". Breast Cancer Res. Treat. 115 (2): 255–68. doi:10.1007/s10549-008-0137-8. PMID 18683044.
  8. ↑ UK Department of Health Commercial Medicines Unit Electronic Medicines Information Tool, London, 2015
  9. ↑ UK’s NICE says no to AstraZeneca breast cancer drug Faslodex, The Pharma Letter, 10 November 2011
  10. ↑ National Institute for Health and Clinical Excellence Guidance Breast cancer (metastatic) - fulvestrant
  11. ↑ Patent Term Extensions The United States Patent and Trademark Office.
  12. ↑ Determination of Regulatory Review Period for Purposes of Patent Extension; FASLODEX A Notice by the Food and Drug Administration on 04/17/2003
  13. ↑ Generic Faslodex Availability, Drugs.COM
  14. ↑ Pink Ribbon Blues: How Breast Cancer Culture Undermines Women's Health By Gayle A. Sulik, Oxford University Press (Oct. 2010)

External links


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