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Oxaliplatin

From Wikipedia, the free encyclopedia
(Redirected fromEloxatin)
Pharmaceutical drug

Pharmaceutical compound
Oxaliplatin
Clinical data
Trade namesEloxatin
AHFS/Drugs.comMonograph
MedlinePlusa607035
License data
Routes of
administration
Intravenous
ATC code
Legal status
Legal status
Pharmacokinetic data
BioavailabilityComplete
Eliminationhalf-life~10 – 25 minutes[4]
ExcretionKidney
Identifiers
  • [(1R,2R)-cyclohexane-1,2-diamine](ethanedioato-O,O')platinum(II)
CAS Number
PubChemCID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
PDB ligand
CompTox Dashboard(EPA)
ECHA InfoCard100.150.118Edit this at Wikidata
Chemical and physical data
FormulaC8H14N2O4Pt
Molar mass397.294 g·mol−1
3D model (JSmol)
  • O1C(=O)C(=O)O[Pt-2]12[NH2+]C0CCCCC0[NH2+]2
 ☒NcheckY (what is this?)  (verify)

Oxaliplatin, sold under the brand nameEloxatin among others, is acancer medication (platinum-based antineoplastic class) used to treatcolorectal cancer.[5] It is given byinfusion into a vein.[5]

Common side effects includenumbness, feeling tired, nausea, diarrhea, andlow blood cell counts.[5][6] Other serious side effects includeallergic reactions.[6][5] Use inpregnancy is known to harm the baby.[5] Oxaliplatin is in theplatinum-based antineoplastic family of medications.[7] It is believed to work by blocking the duplication ofDNA.[5]

Oxaliplatin was patented in 1976 in Japan and approved for medical use in 1996 in Europe.[8] It is on the 2023World Health Organization's List of Essential Medicines.[9]

Medical uses

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Oxaliplatin is used for treatment ofcolorectal cancer, typically along withfolinic acid (leucovorin) andfluorouracil in a combination known asFOLFOX[10] or along withcapecitabine in a combination known asCAPOX[11] orXELOX.[12] It also has uses inpancreatic cancer[13] andstomach cancer oresophageal cancer.[14] It may also be effective againstbreast cancer,germ cell tumor,ovarian cancer andnon-small-cell lung cancer.[15]

Advanced colorectal cancer

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Oxaliplatin by itself has modest activity against advanced colorectal cancer.[16] When compared with just5-fluorouracil andfolinic acid administered according to thede Gramont regimen, a FOLFOX4 regime produced no significant increase in overall survival, but did produce an improvement inprogression-free survival, the primary end-point of the phase III randomized trial.[17]

Adverse effects

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Side-effects of oxaliplatin treatment can potentially include:

In addition, some patients may experience anallergic reaction to platinum-containing drugs. This is more common in women.[21]

Oxaliplatin has less ototoxicity andnephrotoxicity than cisplatin and carboplatin.[18]

Structure and mechanism

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The compound features asquare planar platinum(II) center. In contrast to other drugs of theplatinum-based antineoplastic class of drugscisplatin andcarboplatin, oxaliplatin features thebidentate ligandtrans-1,2-diaminocyclohexane in place of the twomonodentate ammineligands. It also features a bidentateoxalate group.[7] The three-dimensional structure of the molecule has been elucidated by X-ray crystallography, although the presence of pseudosymmetry in the crystal structure has caused confusion in its interpretation.[24]

According toin vivo studies, oxaliplatin fightscarcinoma of thecolon through non-targetedcytotoxic effects. Like other platinum compounds, its cytotoxicity is thought to result from inhibition ofDNA synthesis in cells. In particular, oxaliplatin forms both inter- and intra-strand cross links in DNA,[25] which prevent DNA replication and transcription, causing cell death.

History

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Oxaliplatin was first synthesized in 1978 atNagoya City University by Yoshinori Kidani.[26] It was later developed in Europe as a less toxic and more effective alternative to cisplatin. It gained European approval in 1996,[27] and approval by theU.S. Food and Drug Administration in 2002.[28]Generic oxaliplatin was first approved in the United States in August 2009.[29] Patent disputes caused generic production to stop in 2010, but it restarted in 2012.[30][31]

Patent information

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Eloxatin was covered by patent numbers 5338874 (expired 7 April 2013), 5420319 (expired 8 August 2016), 5716988 (expired 7 August 2015) and 5290961 (expired 12 January 2013) (see Electronic Orange Book patent info for Eloxatin).[32] Exclusivity code I-441, which expired on 4 November 2007, is for use combination with infusional 5-FU/LV for adjuvant treatment stage III colon cancer patients who have undergone complete resection primary tumor-based on improvement in disease free survival with no demonstrated benefit overall survival after 4 years. Exclusivity code NCE, New Chemical Entity, expired on 9 August 2007.[32]

References

[edit]
  1. ^"FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)".nctr-crs.fda.gov.FDA. Retrieved22 October 2023.
  2. ^"Prescription medicines: registration of new generic medicines and biosimilar medicines, 2017".Therapeutic Goods Administration (TGA). 21 June 2022. Retrieved30 March 2024.
  3. ^"Eloxatin- oxaliplatin injection, solution, concentrate".DailyMed. 22 October 2019. Retrieved26 May 2022.
  4. ^Ehrsson H, Wallin I, Yachnin J (2002). "Pharmacokinetics of oxaliplatin in humans".Medical Oncology.19 (4):261–265.doi:10.1385/MO:19:4:261.PMID 12512920.S2CID 1068099.
  5. ^abcdef"Oxaliplatin". The American Society of Health-System Pharmacists.Archived from the original on 21 December 2016. Retrieved8 December 2016.
  6. ^abOun R, Moussa YE, Wheate NJ (May 2018). "The side effects of platinum-based chemotherapy drugs: a review for chemists".Dalton Transactions.47 (19):6645–6653.doi:10.1039/c8dt00838h.PMID 29632935.
  7. ^abApps MG, Choi EH, Wheate NJ (August 2015)."The state-of-play and future of platinum drugs".Endocrine-Related Cancer.22 (4):R219 –R233.doi:10.1530/ERC-15-0237.hdl:2123/24426.PMID 26113607.
  8. ^Fischer J, Ganellin CR (2006).Analogue-based Drug Discovery. John Wiley & Sons. p. 513.ISBN 9783527607495.Archived from the original on 20 December 2016.
  9. ^World Health Organization (2023).The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023). Geneva: World Health Organization.hdl:10665/371090. WHO/MHP/HPS/EML/2023.02.
  10. ^"FOLFOX".National Cancer Institute. 18 September 2009. Retrieved26 May 2022.
  11. ^"CAPOX".National Cancer Institute. 4 April 2012. Retrieved26 May 2022.
  12. ^"XELOX".National Cancer Institute. 6 January 2012. Retrieved26 May 2022.
  13. ^Conroy T, Desseigne F, Ychou M, Bouché O, Guimbaud R, Bécouarn Y, et al. (May 2011)."FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer".The New England Journal of Medicine.364 (19):1817–1825.doi:10.1056/NEJMoa1011923.PMID 21561347.
  14. ^Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, Coxon F, et al. (January 2008)."Capecitabine and oxaliplatin for advanced esophagogastric cancer".The New England Journal of Medicine.358 (1):36–46.doi:10.1056/NEJMoa073149.PMID 18172173.
  15. ^Townsend D (2007). "Oxaliplatin".xPharm: The Comprehensive Pharmacology Reference. Elsevier. pp. 1–4.doi:10.1016/B978-008055232-3.62973-3.ISBN 9780080552323.
  16. ^Bécouarn Y, Ychou M, Ducreux M, Borel C, Bertheault-Cvitkovic F, Seitz JF, et al. (August 1998). "Phase II trial of oxaliplatin as first-line chemotherapy in metastatic colorectal cancer patients. Digestive Group of French Federation of Cancer Centers".Journal of Clinical Oncology.16 (8):2739–2744.doi:10.1200/JCO.1998.16.8.2739.PMID 9704726.
  17. ^de Gramont A, Figer A, Seymour M, Homerin M, Hmissi A, Cassidy J, et al. (August 2000). "Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer".Journal of Clinical Oncology.18 (16):2938–2947.doi:10.1200/JCO.2000.18.16.2938.PMID 10944126.
  18. ^abPasetto LM, D'Andrea MR, Rossi E, Monfardini S (August 2006). "Oxaliplatin-related neurotoxicity: how and why?".Critical Reviews in Oncology/Hematology.59 (2):159–168.doi:10.1016/j.critrevonc.2006.01.001.PMID 16806962.
  19. ^Webster RG, Brain KL, Wilson RH, Grem JL, Vincent A (December 2005)."Oxaliplatin induces hyperexcitability at motor and autonomic neuromuscular junctions through effects on voltage-gated sodium channels".British Journal of Pharmacology.146 (7):1027–1039.doi:10.1038/sj.bjp.0706407.PMC 1751225.PMID 16231011.
  20. ^Gebremedhn EG, Shortland PJ, Mahns DA (April 2018)."The incidence of acute oxaliplatin-induced neuropathy and its impact on treatment in the first cycle: a systematic review".BMC Cancer.18 (1): 410.doi:10.1186/s12885-018-4185-0.PMC 5897924.PMID 29649985.
  21. ^abChay WY, Chew L, Yeoh TT, Tan MH (May 2010)."An association between transient hypokalemia and severe acute oxaliplatin-related toxicity predominantly in women".Acta Oncologica.49 (4):515–517.doi:10.3109/02841860903464015.PMID 20092386.S2CID 33026126.
  22. ^"Oxaliplatin Side Effects".Drugs.com.Archived from the original on 5 September 2014. Retrieved5 September 2014.
  23. ^"Eloxatin information".mein.sanofi.de (in German).Archived from the original on 27 August 2016. Retrieved15 June 2016.
  24. ^Johnstone TC (January 2014)."The Crystal Structure of Oxaliplatin: A Case of Overlooked Pseudo Symmetry".Polyhedron.67:429–435.doi:10.1016/j.poly.2013.10.003.PMC 3885251.PMID 24415827.
  25. ^Graham J, Mushin M, Kirkpatrick P (January 2004). "Oxaliplatin".Nature Reviews. Drug Discovery.3 (1):11–12.doi:10.1038/nrd1287.PMID 14756144.
  26. ^Pizarro AM, Barry NP, Sadler PJ (2013). "3.25 - Metal–DNA Coordination Complexes".Comprehensive Inorganic Chemistry II (2nd ed.). Elsevier. pp. 751–784.doi:10.1016/B978-0-08-097774-4.00330-2.ISBN 9780080965291.
  27. ^Janjan NA, Delclos ME, Crane CH, Krishnan S, Das P (2010). "Chapter 24 - The Colon and Rectum".Radiation Oncology (9th ed.). Mosby. pp. 560–605.ISBN 978-0-323-04971-9.
  28. ^"Eloxatin FDA Approval History".Drugs.com.
  29. ^"Generic Eloxatin availability".Drugs.com.Archived from the original on 7 June 2013. Retrieved19 April 2014.
  30. ^"Hospira Announces U.S. Re-Launch Of Generic Oxaliplatin Injection" (Press release).Archived from the original on 24 September 2015. Retrieved25 August 2015.
  31. ^"Top 10 best-selling cancer drugs: Eloxatin–$1.2 billion".FiercePharma. 15 May 2012.Archived from the original on 21 April 2014. Retrieved20 April 2014.
  32. ^ab"Patent and Exclusivity Search Results from query on Appl No 021759 Product 001 in the OB_Rx list".Orange Book. U.S. Food and Drug Administrartion. Archived fromthe original on 26 September 2007.. Accessed on: 22 July 2007.

Further reading

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External links

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