Fulvestrant

Fulvestrant
Clinical data
Trade names Faslodex
AHFS/Drugs.com Monograph
Pregnancy
category
  • D
Routes of
administration		 Intramuscular injection
ATC code L02BA03 (WHO)
Legal status
Legal status
  • ℞ (Prescription only)
Pharmacokinetic data
Protein binding 99%
Biological half-life 40 days
Identifiers
Synonyms ICI-182,780
CAS Number 129453-61-8 YesY
PubChem (CID) 104741
IUPHAR/BPS 1015
DrugBank DB00947 N
ChemSpider 94553 N
UNII 22X328QOC4 YesY
KEGG D01161 N
ChEBI CHEBI:31638 N
ChEMBL CHEMBL1358 N
Chemical and physical data
Formula C32H47F5O3S
Molar mass 606.772 g/mol
3D model (Jmol) Interactive image
 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.

Clinical trials

Fulvestrant provides effective second-line therapy in metastatic or locally advanced breast cancer for postmenopausal women who relapse or progress after previous endocrine therapy.[4]

Four clinical trials in this setting showed similar efficacy to the other hormonal agents (aromatase inhibitors and tamoxifen) with good tolerability profile. Fulvestrant had a lower incidence of joint disorders.[5][6]

A Phase 2 clinical trial,[7] investigates the use of fulvestrant administered through a microcatheter into the lactiferous duct as neoadjuvant treatment for ductal carcinoma in situ and invasive breast cancer.

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. In the 12 months ending June 2015, the UK price (excluding VAT) of a month's supply of anastrozole (Arimidex), which is off patent, cost 89 pence/day, and letrozole (Femara) cost £1.40/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]

Interference with lab result

Due to the medication having a similar chemical structure to estrogen, it can interact with immunoassays for blood estradiol concentrations and show falsely elevated results.[15] This could improperly lead to medication discontinuation.[15]

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). PMID 21501600.
  4. ↑ 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.
  5. ↑ 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.
  6. ↑ 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.
  7. ↑ "PK Study of Pre-Surgical Intramuscular and Intraductal Fulvestrant in Women With Invasive Breast Cancer or DCIS Undergoing Mastectomy". Clinicaltrials.gov. 28 August 2015.
  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)
  15. 1 2 Estradiol immunoassays – interference from the drug fulvestrant (Faslodex) may cause falsely elevated estradiol results. HMGov, UK.

External links

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