Eribulin

Source: Wikipedia, the free encyclopedia.

Eribulin
Clinical data
Trade namesHalaven, Mevlyq
Other namesE7389, ER-086526, NSC-707389, eribulin mesilate (JAN JP), eribulin mesylate (USAN US)
AHFS/Drugs.comMonograph
MedlinePlusa611007
License data
Pregnancy
category
Antineoplastic agent
ATC code
Legal status
Legal status
Identifiers
  • 2-(3-Amino-2-hydroxypropyl)hexacosahydro-3-methoxy- 26-methyl-20,27-bis(methylene)11,15-18,21-24,28-triepoxy- 7,9-ethano-12,15-methano-9H,15H-furo(3,2-i)furo(2',3'-5,6) pyrano(4,3-b)(1,4)dioxacyclopentacosin-5-(4H)-one
JSmol)
  • CC1CC2CCC3C(=C)CC(O3)CCC45CC6C(O4)C7C(O6)C(O5)C8C(O7)CCC(O8)CC(=O)CC9C(CC(C1=C)O2)OC(C9OC)CC(CN)O
  • InChI=1S/C40H59NO11/c1-19-11-24-5-7-28-20(2)12-26(45-28)9-10-40-17-33-36(51-40)37-38(50-33)39(52-40)35-29(49-37)8-6-25(47-35)13-22(42)14-27-31(16-30(46-24)21(19)3)48-32(34(27)44-4)15-23(43)18-41/h19,23-39,43H,2-3,5-18,41H2,1,4H3/t19-,23+,24+,25-,26+,27+,28+,29+,30-,31+,32-,33-,34-,35+,36+,37+,38-,39+,40+/m1/s1 checkY
  • Key:UFNVPOGXISZXJD-JBQZKEIOSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Eribulin, sold under the brand name Halaven among others, is an

anti-cancer medication used to treat breast cancer and liposarcoma.[4][5]

The most common side effects include fatigue, nausea, hair loss (alopecia), constipation, certain nerve damage causing weakness or numbness in the hands and feet (peripheral neuropathy), abdominal pain and fever (pyrexia).[10] Eribulin may also cause low levels of infection-fighting white blood cells (neutropenia) or decreased levels of potassium or calcium.[10]

Eribulin was approved for medical use in the United States in November 2010,

generic medication.[6]

Medical uses

Eribulin is

indicated for the treatment of people with locally advanced or metastatic breast cancer,[5][14][15][16][17][18] and for the treatment of adults with unresectable liposarcoma.[5][10][19]

Adverse effects

Serious side effects may include anaemia; decrease in white blood cell count, which can increase the risk of serious infections that could lead to death; hair loss; cancer-related fatigue; numbness, tingling or burning in the hands and feet (neuropathy); harm to a developing fetus; as well as changes in heartbeat (QTc prolongation), that may also lead to death.[10][20][unreliable medical source?]

Structure and mechanism

Eribulin is a fully synthetic

analog of the marine natural product halichondrin B,[21][22] the parent molecule being a naturally occurring, potent mitotic inhibitor with a unique mechanism of action. The parent molecule was originally found in the sponge Halichondria okadai.[23][24]

Eribulin is a mechanistically unique inhibitor of microtubule dynamics,[25][26] binding predominantly to a small number of high affinity sites at the plus ends of existing microtubules.[27][28] Eribulin has both cytotoxic and non-cytotoxic mechanisms of action. Its cytotoxic effects are related to its antimitotic activities, wherein

epithelial-mesenchymal transition (EMT), and decreased capacity for migration and invasion leading to reduced metastatic capacity as measured in a preclinical experimental metastasis model.[31][32] In other studies, eribulin treatment of leiomyosarcoma and liposarcoma cells leads to increased expression of smooth muscle and adipocyte differentiation antigens, respectively.[33] Taxane-resistant cancers are often unresponsive to eribulin. A recent study found that this resistance is due to expression of multidrug resistance protein 1 (MDR1).[34] Fluorescently labeled eribulin has been used to study the pharmacokinetics and pharmacodynamics at single cell level in vivo.[34]

The synthesis of eribulin was first published[35] in 2001; a new synthetic route to the drug was published in 2009.[36]

Research

Eribulin is being investigated for use in a variety of solid tumors, including

non-small cell lung cancer, prostate cancer, brain cancer, cervical cancer, urothelial cancer, melanoma, solitary fibrous tumors, and various sarcomas.[37]

Two eribulin based products are in the research and development phase; a liposomal formulation and antibody drug combination therapy, both are for the treatment of solid tumors. The liposomal formulation of eribulin, E7389 liposomal, is in Phase I clinical trials.

PD-1 inhibitor, for the treatment of breast cancer and other advanced cancers.[40]

References

  1. ^ "Eribulin (Halaven) Use During Pregnancy". Drugs.com. 22 October 2019. Retrieved 9 July 2020.
  2. ^ a b "Halaven Product information". Health Canada. 22 October 2009. Retrieved 16 December 2023.
  3. ^ "Halaven 0.44 mg/ml solution for injection". (emc). 16 January 2023. Retrieved 16 December 2023.
  4. ^ a b "Halaven- eribulin mesylate injection". DailyMed. 22 December 2017. Retrieved 9 July 2020.
  5. ^ a b c d e "Halaven EPAR". European Medicines Agency (EMA). 17 March 2011. Retrieved 16 December 2023.
  6. ^ a b "Mevlyq EPAR". European Medicines Agency (EMA). 9 February 2024. Retrieved 19 February 2024.
  7. ^ "Mevlyq product information". Union Register of medicinal products. 13 February 2024. Retrieved 19 February 2024.
  8. ^ "Eisai Announces Japan Launch Of Anticancer Agent Halaven" (Press release). Eisai Co., Ltd. 19 July 2011. Retrieved 15 February 2021.
  9. ^ "Anticancer Agent Halaven Approved For Treatment Of Locally Advanced Or Metastatic Breast Cancer In China" (Press release). Eisai Co., Ltd. 17 July 2019. Retrieved 15 February 2021.
  10. ^ a b c d "FDA approves first drug to show survival benefit in liposarcoma". U.S. Food and Drug Administration (FDA) (Press release). 28 January 2016. Retrieved 9 July 2020. Public Domain This article incorporates text from this source, which is in the public domain.
  11. ^ "Drug Approval Package: Halaven (erbulin mesylate) NDA 201532". U.S. Food and Drug Administration (FDA). Retrieved 9 July 2020.
  12. ^ "Halaven for Metastatic Breast Cancer". Canadian Agency for Drugs and Technologies in Health. 9 March 2015. Retrieved 9 July 2020.
  13. ^ "Eisai Announces Canadian Approval of its Anticancer Agent Halaven". Eisai Co., Ltd. (Press release). Retrieved 9 July 2020.
  14. ^ "FDA approves new treatment option for late-stage breast cancer" (Press release). U.S. Food and Drug Administration (FDA). 15 November 2010. Archived from the original on 17 November 2010. Retrieved 15 November 2010.
  15. ^ "Eribulin". U.S. Food and Drug Administration. 28 January 2016. Retrieved 16 December 2023.
  16. ^ Notice of Decision for Halaven[permanent dead link]
  17. ^ "Halaven for Metastatic Breast Cancer". Canadian Agency for Drugs and Technologies in Health. 9 March 2015. Retrieved 9 July 2020.
  18. ^ "Eisai Announces Canadian Approval of its Anticancer Agent Halaven". Eisai Co., Ltd. (Press release). Retrieved 9 July 2020.
  19. ^ "U.S. FDA Approves Eisai's Anticancer Agent Halaven For The Treatment Of Advanced Liposarcoma" (Press release). Eisai Co., Ltd. 29 January 2016. Retrieved 15 February 2021.
  20. ^ "Eribulin (Halaven)". Breast Cancer Now. 5 June 2015. Retrieved 15 September 2022.
  21. PMID 11221827
    .
  22. ISBN 978-0-8493-1863-4.[page needed
    ]
  23. S2CID 38138047
    .
  24. PMID 1874739
    .
  25. S2CID 38459382
    .
  26. PMID 18645010
    .
  27. PMID 20030375
    .
  28. PMID 26435331
    .
  29. S2CID 30919443
    .
  30. PMID 21127197
    .
  31. PMID 25060424
    .
  32. PMID 24569463
    .
  33. PMID 27069131
    .
  34. ^
    PMID 25378644
    .
  35. PMID 15482921
    .
  36. PMID 19807076
    .
  37. ^ "184 Studies found for: eribulin OR E7389". ClinicalTrials.gov. U.S. National Library of Medicine.
  38. ^ Clinical trial number NCT03207672 for "Study of E7389 Liposomal Formulation in Subjects With Solid Tumor" at ClinicalTrials.gov
  39. PMID 23313921
    .
  40. ^ Clinical trial number NCT03222856 for "Ph II Study of Pembrolizumab & Eribulin in Patients With HR+/HER2- MBC Previously Treated With Anthracyclines & Taxanes (KELLY)" at ClinicalTrials.gov
Retrieved from "https://en.wikipedia.org/w/index.php?title=Eribulin&oldid=1208833893"