Fulvestrant

Last updated
Fulvestrant
Fulvestrant.svg
Clinical data
Pronunciation /fʊlˈvɛstrənt/
fuul-VES-trənt
Trade names Faslodex, others
Other namesICI-182780; ZD-182780; ZD-9238; 7α-[9-[(4,4,5,5,5-Pentafluoropentyl)-sulfinyl]nonyl]estra-1,3,5(10)-triene-3,17β-diol
AHFS/Drugs.com Monograph
License data
Pregnancy
category
  • AU:D
  • D
Routes of
administration 		Intramuscular injection
Drug class Antiestrogen
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • US: ℞-only
  • EU:Rx-only
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability Low [1]
Protein binding 99% [1]
Metabolism Hydroxylation, conjugation (glucuronidation, sulfation) [1]
Elimination half-life IM Tooltip Intramuscular injection: 40–50 days [1]
Identifiers
  • (7R,8R,9S,13S,14S,17S)-13-methyl-7-[9-(4,4,5,5,5-pentafluoropentylsulfinyl)nonyl]-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthrene-3,17-diol
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.170.955 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C32H47F5O3S
Molar mass 606.78 g·mol−1
3D model (JSmol)
  • C[C@]12CC[C@@H]3c4ccc(O)cc4CC(CCCCCCCCCS(=O)CCCC(F)(F)C(F)(F)F)[C@H]3[C@@H]1CC[C@@H]2O
  • InChI=1S/C32H47F5O3S/c1-30-17-15-26-25-12-11-24(38)21-23(25)20-22(29(26)27(30)13-14-28(30)39)10-7-5-3-2-4-6-8-18-41(40)19-9-16-31(33,34)32(35,36)37/h11-12,21-22,26-29,38-39H,2-10,13-20H2,1H3/t22-,26-,27+,28+,29-,30+,41?/m1/s1
  • Key:VWUXBMIQPBEWFH-WCCTWKNTSA-N
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Fulvestrant, sold under the brand name Faslodex among others, is an antiestrogenic medication used to treat hormone receptor (HR)-positive metastatic breast cancer in postmenopausal women with disease progression as well as HR-positive, HER2-negative advanced breast cancer in combination with abemaciclib or palbociclib in women with disease progression after endocrine therapy. [2] It is given by injection into a muscle. [3]

Contents

Fulvestrant is a selective estrogen receptor degrader (SERD) and was first-in-class to be approved. [4] It works by binding to the estrogen receptor and destabilizing it, causing the cell's normal protein degradation processes to destroy it. [4]

Fulvestrant was approved for medical use in the United States in 2002. [5]

Medical uses

Breast cancer

Fulvestrant is used for the treatment of hormone receptor positive metastatic breast cancer or locally advanced unresectable disease in postmenopausal women; it is given by injection. [3] A 2017 Cochrane review found it is as safe and effective as first line or second line endocrine therapy. [3]

It is also used to treat ER-positive, HER2-negative advanced or metastatic breast cancer in combination with abemaciclib or palbociclib in women with disease progression after first-line endocrine therapy. [2]

Due to the medication's having a chemical structure similar to that of estrogen, it can interact with immunoassays for blood estradiol concentrations and show falsely elevated results. [6] [7] [8] This can improperly lead to discontinuing the treatment. [6]

Early puberty

Fulvestrant has been used in the treatment of peripheral precocious puberty in girls with McCune–Albright syndrome. [9] [10] [11]

Available forms

Fulvestrant is provided in a castor oil solution also containing alcohol, benzyl alcohol, and benzyl benzoate. [2] It is supplied at a concentration of 250 mg/5 mL. [2]

Contraindications

Fulvestrant should not be used in women with kidney failure or who are pregnant. [2] [12]

Side effects

Very common (occurring in more than 10% of people) adverse effects include nausea, injection site reactions, weakness, and elevated transaminases. Common (between 1% and 10%) adverse effects include urinary tract infections, hypersensitivity reactions, loss of appetite, headache, blood clots in veins, hot flushes, vomiting, diarrhea, elevated bilirubin, rashes, and back pain. [12] In a large clinical trial, the incidence of venous thromboembolism (VTE) with fulvestrant was 0.9%. [2]

Pharmacology

Pharmacodynamics

Fulvestrant is an antiestrogen which acts as an antagonist of the estrogen receptor (ER) and additionally as a selective estrogen receptor degrader (SERD). [4] It works by binding to the estrogen receptor and making it more hydrophobic, which makes the receptor unstable and misfold, which in turn leads normal processes inside the cell to degrade it. [4]

In addition to its antiestrogenic activity, fulvestrant is an agonist of the G protein-coupled estrogen receptor (GPER), albeit with relatively low affinity (10–100 nM, relative to 3–6 nM for estradiol). [13] [14] [15] [16] [17]

Pharmacokinetics

Fulvestrant after an intramuscular injection is slowly absorbed and maximal levels (Cmax) are reached after 5 days on average with a range of 2 to 19 days. [18] The elimination half-life of fulvestrant with intramuscular injection is 40 to 50 days. [19] [2] This is 40 times longer than the half-life of fulvestrant by intravenous injection, indicating that its long half-life with intramuscular injection is due to slow absorption from the injection site. [18] Levels of fulvestrant with 500 mg/month by intramuscular injection (and a single additional 500 mg loading dose on day 15 of therapy) in postmenopausal women with advanced breast cancer were 25.1 ng/mL (25,100 pg/mL) at peak and 28.0 ng/mL (28,000 pg/mL) at trough with a single dose and 28.0 ng/mL (28,000 pg/mL) at peak and 12.2 ng/mL (12,200 pg/mL) at trough after multiple doses at steady state. [2]

Fulvestrant does not cross the blood–brain barrier in animals and may not in humans as well. [20] [21] [22] Accordingly, no effects of fulvestrant on brain function have been observed in preclinical or clinical research. [21] [22] Fulvestrant is highly (99%) bound to plasma proteins. [19] [2] It is bound to very low density lipoprotein, low density lipoprotein, and high density lipoprotein, but not to sex hormone-binding globulin. [19]

Fulvestrant appears to be metabolized along similar pathways as endogenous steroids; CYP3A4 may be involved, but non-cytochrome P450 routes appear to be more important. It does not inhibit any cytochrome P450 enzymes. Elimination is almost all via feces. [12]

Fulvestrant can form colloidal aggregates at certain concentration ranges and this can limit its activity as well as produce bell-shaped concentration–response curves. [23] [24] [25]

Chemistry

Fulvestrant, also known as 7α-[9-[(4,4,5,5,5-pentafluoropentyl)sulfinyl]nonyl]estradiol, is a synthetic estrane steroid and a derivative of estradiol. An alkyl-sulfinyl moiety was added to the endogenous estrogen receptor ligand. [4]

It was discovered through rational drug design, but was selected for further development via phenotypic screening. [26]

History

Fulvestrant was the first selective estrogen receptor degrader to be approved. [4] It was approved in the United States in 2002 [2] and in Europe in 2004. [12]

Society and culture

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.[ citation needed ] 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. [27] [28] [29]

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. [30] [31] AstraZeneca has filed later patents. A generic version of Faslodex has been approved by the FDA. However, this does not mean that the product will necessarily be commercially available - possibly because of drug patents and/or drug exclusivity. [32] A later patent for Faslodex expires in January 2021. [33] Atossa Genetics has a patent for the administration of fulvestrant into the breast via a microcatheter invented by Susan Love. [34]

Research

Fulvestrant was studied in endometrial cancer but results were not promising and as of 2016 development for this use was abandoned. [35]

Because fulvestrant cannot be given orally, efforts have been made to develop SERD drugs that can be taken by mouth, including brilanestrant and elacestrant. [4] The clinical success of fulvestrant also led to efforts to discover and develop a parallel drug class of selective androgen receptor degraders (SARDs). [4]

ZB716, or fulvestrant-3-boronic acid, is an oral prodrug of fulvestrant which is under development. [36] [37] [38]

Related Research Articles

<span class="mw-page-title-main">Selective estrogen receptor modulator</span> Drugs acting on the estrogen receptor

Selective estrogen receptor modulators (SERMs), also known as estrogen receptor agonist/antagonists (ERAAs), are a class of drugs that act on the estrogen receptor (ER). A characteristic that distinguishes these substances from pure ER agonists and antagonists is that their action is different in various tissues, thereby granting the possibility to selectively inhibit or stimulate estrogen-like action in various tissues.

<span class="mw-page-title-main">Raloxifene</span> Chemical compound

Raloxifene, sold under the brand name Evista among others, is a medication used to prevent and treat osteoporosis in postmenopausal women and those on glucocorticoids. For osteoporosis it is less preferred than bisphosphonates. It is also used to reduce the risk of breast cancer in those at high risk. It is taken by mouth.

<span class="mw-page-title-main">Lasofoxifene</span> Chemical compound

Lasofoxifene, sold under the brand name Fablyn, is a nonsteroidal selective estrogen receptor modulator (SERM) which is marketed by Pfizer in Lithuania and Portugal for the prevention and treatment of osteoporosis and for the treatment of vaginal atrophy, and the result of an exclusive research collaboration with Ligand Pharmaceuticals (LGND). It also appears to have had a statistically significant effect of reducing breast cancer in women according to a study published in The Journal of the National Cancer Institute.

<span class="mw-page-title-main">GPER</span> Protein-coding gene in the species Homo sapiens

G protein-coupled estrogen receptor 1 (GPER), also known as G protein-coupled receptor 30 (GPR30), is a protein that in humans is encoded by the GPER gene. GPER binds to and is activated by the female sex hormone estradiol and is responsible for some of the rapid effects that estradiol has on cells.

Antiestrogens, also known as estrogen antagonists or estrogen blockers, are a class of drugs which prevent estrogens like estradiol from mediating their biological effects in the body. They act by blocking the estrogen receptor (ER) and/or inhibiting or suppressing estrogen production. Antiestrogens are one of three types of sex hormone antagonists, the others being antiandrogens and antiprogestogens. Antiestrogens are commonly used to stop steroid hormones, estrogen, from binding to the estrogen receptors leading to the decrease of estrogen levels. Decreased levels of estrogen can lead to complications in sexual development. Antiandrogens are sex hormone antagonists which are able to lower the production and the effects that testosterone can have on female bodies.

Antihormone therapy is a type of hormone therapy that suppresses selected hormones or their effects, in contrast with hormone replacement therapy, which encourages hormone activity.

<span class="mw-page-title-main">Estradiol cypionate</span> Chemical compound

Estradiol cypionate (EC), sold under the brand name Depo-Estradiol among others, is an estrogen medication which is used in hormone therapy for menopausal symptoms and low estrogen levels in women, in hormone therapy for trans women, and in hormonal birth control for women. It is given by injection into muscle once every 1 to 4 weeks.

<span class="mw-page-title-main">Estradiol dipropionate</span> Chemical compound

Estradiol dipropionate (EDP), sold under the brand names Agofollin, Di-Ovocylin, and Progynon DP among others, is an estrogen medication which has been used in hormone therapy for menopausal symptoms and low estrogen levels in women and in the treatment of gynecological disorders. It has also been used in feminizing hormone therapy for transgender women and in the treatment of prostate cancer in men. Although widely used in the past, estradiol dipropionate has largely been discontinued and is mostly no longer available today. It appears to remain in use only in Japan, Macedonia, and Australia. Estradiol dipropionate is given by injection into muscle at intervals ranging from once or twice a week to once every week and a half to two weeks.

<span class="mw-page-title-main">Buparlisib</span> Chemical compound

Buparlisib is an experimental anti-cancer medication. It is a small molecule orally-available pan-class I phosphoinositide 3-kinase (PI3K) inhibitor. Buparlisib was under investigation as a treatment for advanced breast cancer but was abandoned due to negative results. It is still under investigation as a potential treatment for head and neck squamous cell carcinoma (HNSCC).

A selective estrogen receptor degrader or downregulator (SERD) is a type of drug which binds to the estrogen receptor (ER) and, in the process of doing so, causes the ER to be degraded and thus downregulated. They are used to treat estrogen receptor-sensitive or progesterone receptor-sensitive breast cancer, along with older classes of drugs like selective estrogen receptor modulators (SERMs) and aromatase inhibitors.

<span class="mw-page-title-main">Brilanestrant</span> Discontinued oral cancer remedy

Brilanestrant (INN) is a nonsteroidal combined selective estrogen receptor modulator (SERM) and selective estrogen receptor degrader (SERD) that was discovered by Aragon Pharmaceuticals and was under development by Genentech for the treatment of locally advanced or metastatic estrogen receptor (ER)-positive breast cancer.

<span class="mw-page-title-main">Elacestrant</span> Chemical compound

Elacestrant, sold under the brand name Orserdu, is an anticancer medication which is used in the treatment of breast cancer. It is taken by mouth.

<span class="mw-page-title-main">Etacstil</span> Chemical compound

Etacstil is an orally active, nonsteroidal, combined selective estrogen receptor modulator (SERM) and selective estrogen receptor degrader (SERD) that was developed for the treatment of estrogen receptor-positive breast cancer. It was shown to overcome antiestrogen resistance in breast cancer by altering the shape of the estrogen receptor, thus exhibiting SERD properties. Etacstil is a tamoxifen derivative and one of the first drugs to overcome tamoxifen-resistance. It is the predecessor of GW-7604, of which etacstil is a prodrug. This is analogous to the case of tamoxifen being a prodrug of afimoxifene (4-hydroxytamoxifen).

<span class="mw-page-title-main">Endoxifen</span> Chemical compound

Endoxifen, also known as 4-hydroxy-N-desmethyltamoxifen, is a nonsteroidal selective estrogen receptor modulator (SERM) of the triphenylethylene group as well as a protein kinase C (PKC) inhibitor. It is under development for the treatment of estrogen receptor-positive breast cancer and for the treatment of mania in bipolar disorder. It is taken by mouth.

<span class="mw-page-title-main">MIBE</span> Chemical compound

MIBE is a synthetic, nonsteroidal antiestrogen that acts as a dual antagonist of the ERα and the GPER. It was found to prevent estradiol-induced proliferation of MCF-7 breast cancer cells, an action that was mediated via inhibition of both receptors. The drug was synthesized in 2012. It has been suggested that drugs like MIBE might be superior agents in the treatment of breast cancer compared to current antiestrogens like tamoxifen and fulvestrant, which are antagonistic at the ERα but were found in 2005 to be GPER agonists.

ZB716, also known as fulvestrant-3-boronic acid, is a synthetic, steroidal, orally active antiestrogen which is under development for the treatment of estrogen receptor (ER)-positive metastatic breast cancer. The drug is a silent antagonist of the ERα (IC50 = 4.1 nM) as well as a selective estrogen receptor degrader (SERD). It is an analogue and prodrug of fulvestrant in which the C3 hydroxyl group has been replaced with a boronic acid moiety. In accordance, the two drugs have similar pharmacodynamic properties. However, whereas fulvestrant is not orally active and must be administered via intramuscular injection, ZB716 is less susceptible to first-pass metabolism, and in relation to this, is orally active.

<span class="mw-page-title-main">Estrogen (medication)</span> Type of medication

An estrogen (E) is a type of medication which is used most commonly in hormonal birth control and menopausal hormone therapy, and as part of feminizing hormone therapy for transgender women. They can also be used in the treatment of hormone-sensitive cancers like breast cancer and prostate cancer and for various other indications. Estrogens are used alone or in combination with progestogens. They are available in a wide variety of formulations and for use by many different routes of administration. Examples of estrogens include bioidentical estradiol, natural conjugated estrogens, synthetic steroidal estrogens like ethinylestradiol, and synthetic nonsteroidal estrogens like diethylstilbestrol. Estrogens are one of three types of sex hormone agonists, the others being androgens/anabolic steroids like testosterone and progestogens like progesterone.

<span class="mw-page-title-main">Pharmacokinetics of estradiol</span>

The pharmacology of estradiol, an estrogen medication and naturally occurring steroid hormone, concerns its pharmacodynamics, pharmacokinetics, and various routes of administration.

Endocrine therapy is a common treatment for estrogen receptor positive breast cancer. However, resistance to this therapy can develop, leading to relapse and progression of disease. This highlights the need for new strategies to combat this resistance.

References

  1. 1 2 3 4 Dörwald FZ (4 February 2013). Lead Optimization for Medicinal Chemists: Pharmacokinetic Properties of Functional Groups and Organic Compounds. John Wiley & Sons. pp. 486–. ISBN   978-3-527-64565-7.
  2. 1 2 3 4 5 6 7 8 9 10 "US Label: Fulvestrant" (PDF). FDA. July 2016.
  3. 1 2 3 Lee CI, Goodwin A, Wilcken N (January 2017). "Fulvestrant for hormone-sensitive metastatic breast cancer". The Cochrane Database of Systematic Reviews. 1 (1): CD011093. doi:10.1002/14651858.CD011093.pub2. PMC   6464820 . PMID   28043088.
  4. 1 2 3 4 5 6 7 8 Lai AC, Crews CM (February 2017). "Induced protein degradation: an emerging drug discovery paradigm". Nature Reviews. Drug Discovery. 16 (2): 101–114. doi:10.1038/nrd.2016.211. PMC   5684876 . PMID   27885283.
  5. ↑ "Fulvestrant". The American Society of Health-System Pharmacists. Retrieved 8 January 2017.
  6. 1 2 "Estradiol immunoassays – interference from the drug fulvestrant (Faslodex®) may cause falsely elevated estradiol results Medical safety alert - GOV.UK". UK Medicines and Healthcare products Regulatory Agency. 24 March 2016. Archived from the original on 19 July 2017. Retrieved 2 May 2016.
  7. ↑ Owen LJ, Monaghan PJ, Armstrong A, Keevil BG, Higham C, Salih Z, Howell S (February 2019). "Oestradiol measurement during fulvestrant treatment for breast cancer". Br J Cancer. 120 (4): 404–406. doi:10.1038/s41416-019-0378-9. PMC   6461991 . PMID   30679781.
  8. ↑ Samuel E, Chiang C, Jennens R, Faulkner D, Francis PA (February 2020). "Fulvestrant falsely elevates oestradiol levels in immunoassays in postmenopausal women with breast cancer". Eur J Cancer. 126: 104–105. doi:10.1016/j.ejca.2019.10.015. PMID   31927211. S2CID   210166996.
  9. ↑ Fuqua JS (June 2013). "Treatment and outcomes of precocious puberty: an update". The Journal of Clinical Endocrinology and Metabolism. 98 (6): 2198–207. doi: 10.1210/jc.2013-1024 . PMID   23515450.
  10. ↑ Zacharin M (May 2019). "Disorders of Puberty: Pharmacotherapeutic Strategies for Management". Pediatric Pharmacotherapy. Handbook of Experimental Pharmacology. Vol. 261. Springer. pp. 507–538. doi:10.1007/164_2019_208. ISBN   978-3-030-50493-9. PMID   31144045. S2CID   169040406.
  11. ↑ Sims EK, Garnett S, Guzman F, Paris F, Sultan C, Eugster EA (September 2012). "Fulvestrant treatment of precocious puberty in girls with McCune-Albright syndrome". International Journal of Pediatric Endocrinology. 2012 (1): 26. doi: 10.1186/1687-9856-2012-26 . PMC   3488024 . PMID   22999294.
  12. 1 2 3 4 "Faslodex 250 mg solution for injection - Summary of Product Characteristics". UK Electronic Medicines Compendium. 21 July 2016.
  13. ↑ Prossnitz ER, Arterburn JB (July 2015). "International Union of Basic and Clinical Pharmacology. XCVII. G Protein-Coupled Estrogen Receptor and Its Pharmacologic Modulators". Pharmacol. Rev. 67 (3): 505–40. doi:10.1124/pr.114.009712. PMC   4485017 . PMID   26023144.
  14. ↑ Thomas P, Pang Y, Filardo EJ, Dong J (February 2005). "Identity of an estrogen membrane receptor coupled to a G protein in human breast cancer cells". Endocrinology. 146 (2): 624–32. doi: 10.1210/en.2004-1064 . PMID   15539556.
  15. ↑ Prossnitz ER, Barton M (August 2011). "The G-protein-coupled estrogen receptor GPER in health and disease". Nat Rev Endocrinol. 7 (12): 715–26. doi:10.1038/nrendo.2011.122. PMC   3474542 . PMID   21844907.
  16. ↑ Prossnitz ER, Barton M (May 2014). "Estrogen biology: new insights into GPER function and clinical opportunities". Mol. Cell. Endocrinol. 389 (1–2): 71–83. doi:10.1016/j.mce.2014.02.002. PMC   4040308 . PMID   24530924.
  17. ↑ Barton M (August 2012). "Position paper: The membrane estrogen receptor GPER--Clues and questions". Steroids. 77 (10): 935–42. doi: 10.1016/j.steroids.2012.04.001 . PMID   22521564. S2CID   35909008.
  18. 1 2 Robertson JF, Harrison M (March 2004). "Fulvestrant: pharmacokinetics and pharmacology". Br J Cancer. 90 (Suppl 1): S7–10. doi:10.1038/sj.bjc.6601630. PMC   2750771 . PMID   15094758.
  19. 1 2 3 Croxtall JD, McKeage K (February 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. S2CID   249870430.
  20. ↑ Robertson JF (November 2001). "ICI 182,780 (Fulvestrant)--the first oestrogen receptor down-regulator--current clinical data". Br. J. Cancer. 85 (Suppl 2): 11–4. doi:10.1054/bjoc.2001.1982 (inactive 31 January 2024). PMC   2375169 . PMID   11900210.{{cite journal}}: CS1 maint: DOI inactive as of January 2024 (link)
  21. 1 2 Howell A, Abram P (2005). "Clinical development of fulvestrant ("Faslodex")". Cancer Treat. Rev. 31 (Suppl 2): S3–9. doi:10.1016/j.ctrv.2005.08.010. PMID   16198055.
  22. 1 2 Bundred N, Howell A (April 2002). "Fulvestrant (Faslodex): current status in the therapy of breast cancer". Expert Rev Anticancer Ther. 2 (2): 151–60. doi:10.1586/14737140.2.2.151. PMID   12113237. S2CID   20294814.
  23. ↑ Ganesh AN, Donders EN, Shoichet BK, Shoichet MS (April 2018). "Colloidal aggregation: from screening nuisance to formulation nuance". Nano Today. 19: 188–200. doi:10.1016/j.nantod.2018.02.011. PMC   6150470 . PMID   30250495.
  24. ↑ Ganesh AN, Aman A, Logie J, Barthel BL, Cogan P, Al-Awar R, Koch TH, Shoichet BK, Shoichet MS (April 2019). "Colloidal Drug Aggregate Stability in High Serum Conditions and Pharmacokinetic Consequence". ACS Chem Biol. 14 (4): 751–757. doi:10.1021/acschembio.9b00032. PMC   6474797 . PMID   30840432.
  25. ↑ Owen SC, Doak AK, Ganesh AN, Nedyalkova L, McLaughlin CK, Shoichet BK, Shoichet MS (March 2014). "Colloidal drug formulations can explain "bell-shaped" concentration-response curves". ACS Chem Biol. 9 (3): 777–84. doi:10.1021/cb4007584. PMC   3985758 . PMID   24397822.
  26. ↑ Moffat JG, Rudolph J, Bailey D (August 2014). "Phenotypic screening in cancer drug discovery - past, present and future". Nature Reviews. Drug Discovery. 13 (8): 588–602. doi:10.1038/nrd4366. PMID   25033736. S2CID   5964541.
  27. ↑ UK Department of Health Commercial Medicines Unit Electronic Medicines Information Tool, London, 2015
  28. ↑ UK’s NICE says no to AstraZeneca breast cancer drug Faslodex, The Pharma Letter, 10 November 2011
  29. ↑ National Institute for Health and Clinical Excellence Guidance Archived 2011-04-03 at the Wayback Machine Breast cancer (metastatic) - fulvestrant
  30. ↑ Patent Term Extensions The United States Patent and Trademark Office.
  31. ↑ Determination of Regulatory Review Period for Purposes of Patent Extension; FASLODEX A Notice by the Food and Drug Administration on 04/17/2003
  32. ↑ Generic Faslodex Availability, Drugs.COM
  33. ↑ Pink Ribbon Blues: How Breast Cancer Culture Undermines Women's Health By Gayle A. Sulik, Oxford University Press (Oct. 2010)
  34. ↑ USgranted 6638727,Hung DT, Love S,"Methods for identifying treating or monitoring asymptomatic patients for risk reduction or therapeutic treatment of breast cancer",issued 28 October 2003, assigned to Cytyc Health Corp
  35. ↑ Battista MJ, Schmidt M (2016). "Fulvestrant for the treatment of endometrial cancer". Expert Opinion on Investigational Drugs. 25 (4): 475–83. doi:10.1517/13543784.2016.1154532. PMID   26882357. S2CID   207477738.
  36. ↑ Ahmad, I., Mathew, S., & Rahman, S. (2020). Recent progress in selective estrogen receptor downregulators (SERDs) for the treatment of breast cancer. RSC Medicinal Chemistry, 11(4), 438–454. https://doi.org/10.1039/C9MD00570F
  37. ↑ Liu J, Zheng S, Akerstrom VL, Yuan C, Ma Y, Zhong Q, Zhang C, Zhang Q, Guo S, Ma P, Skripnikova EV, Bratton MR, Pannuti A, Miele L, Wiese TE, Wang G (2016). "Fulvestrant-3 Boronic Acid (ZB716): An Orally Bioavailable Selective Estrogen Receptor Downregulator (SERD)". J. Med. Chem. 59 (17): 8134–40. doi:10.1021/acs.jmedchem.6b00753. PMC   5499704 . PMID   27529700.
  38. ↑ ClinicalTrials.gov: NCT04669587
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.