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Oxaliplatin

December 15, 2023

Oxaliplatin, sold under the brand name Eloxatin among others, is a cancer medication (platinum-based antineoplastic class) used to treat colorectal cancer.[4] It is given by injection into a vein.[4]

Oxaliplatin
Clinical data
Trade namesEloxatin
AHFS/Drugs.comMonograph
MedlinePlusa607035
License data
Routes of
administration		Intravenous
ATC code
Legal status
Legal status
Pharmacokinetic data
BioavailabilityComplete
Elimination half-life~10 – 25 minutes[3]
ExcretionKidney
Identifiers
  • [(1R,2R)-cyclohexane-1,2-diamine](ethanedioato-O,O')platinum(II)
CAS Number
  • 61825-94-3 N
PubChem CID
  • 77994
DrugBank
  • DB00526 N
ChemSpider
  • 8062727 N
UNII
  • 04ZR38536J
KEGG
  • D01790 Y
ChEMBL
  • ChEMBL414804 N
PDB ligand
  • 1PT (PDBe, RCSB PDB)
CompTox Dashboard (EPA)
  • DTXSID0036760
ECHA InfoCard100.150.118
Chemical and physical data
FormulaC8H14N2O4Pt
Molar mass397.294 g·mol−1
3D model (JSmol)
  • Interactive image
  • O1C(=O)C(=O)O[Pt-2]12[NH2+]C0CCCCC0[NH2+]2
 NY (what is this?)  (verify)

Common side effects include numbness, feeling tired, nausea, diarrhea, and low blood cell counts.[4][5] Other serious side effects include allergic reactions.[5][4] Use in pregnancy is known to harm the baby.[4] Oxaliplatin is in the platinum-based antineoplastic family of medications.[6] It is believed to work by blocking the duplication of DNA.[4]

Oxaliplatin was patented in 1976 in Japan and approved for medical use in 1996 in Europe.[7] It is on the 2023 World Health Organization's List of Essential Medicines.[8]

Medical uses edit

Oxaliplatin is used for treatment of colorectal cancer, typically along with folinic acid (leucovorin) and fluorouracil in a combination known as FOLFOX[9] or along with capecitabine in a combination known as CAPOX[10] or XELOX.[11] It may also be effective against breast cancer, germ cell tumor, ovarian cancer, non-small-cell lung cancer, and pancreatic cancer.[12]

Advanced colorectal cancer edit

Oxaliplatin by itself has modest activity against advanced colorectal cancer.[13] When compared with just 5-fluorouracil and folinic acid administered according to the de Gramont regimen, a FOLFOX4 regime produced no significant increase in overall survival, but did produce an improvement in progression-free survival, the primary end-point of the phase III randomized trial.[14]

Adverse effects edit

Side-effects of oxaliplatin treatment can potentially include:

In addition, some patients may experience an allergic reaction to platinum-containing drugs. This is more common in women.[18]

Oxaliplatin has less ototoxicity and nephrotoxicity than cisplatin and carboplatin.[15]

Structure and mechanism edit

The compound features a square planar platinum(II) center. In contrast to other drugs of the platinum-based antineoplastic class of drugs cisplatin and carboplatin, oxaliplatin features the bidentate ligand trans-1,2-diaminocyclohexane in place of the two monodentate ammine ligands. It also features a bidentate oxalate group.[6] 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.[21]

According to in vivo studies, oxaliplatin fights carcinoma of the colon through non-targeted cytotoxic effects. Like other platinum compounds, its cytotoxicity is thought to result from inhibition of DNA synthesis in cells. In particular, oxaliplatin forms both inter- and intra-strand cross links in DNA,[22] which prevent DNA replication and transcription, causing cell death.

History edit

Oxaliplatin was first synthesized in 1978 at Nagoya City University by Yoshinori Kidani.[23] It was later developed in Europe as a less toxic and more effective alternative to cisplatin. It gained European approval in 1996,[24] and approval by the U.S. Food and Drug Administration in 2002.[25] Generic oxaliplatin was first approved in the United States in August 2009.[26] Patent disputes caused generic production to stop in 2010, but it restarted in 2012.[27][28]

Patent information edit

Eloxatin was covered by patent numbers 5338874 (expired April 7, 2013), 5420319 (expired August 8, 2016), 5716988 (expired August 7, 2015) and 5290961 (expired January 12, 2013) (see Electronic Orange Book patent info for Eloxatin).[29] Exclusivity code I-441, which expired on November 4, 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 August 9, 2007.[29]

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. Retrieved 22 Oct 2023.
  2. ^ "Eloxatin- oxaliplatin injection, solution, concentrate". DailyMed. 22 October 2019. Retrieved 26 May 2022.
  3. ^ 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.
  4. ^ a b c d e f "Oxaliplatin". The American Society of Health-System Pharmacists. from the original on 21 December 2016. Retrieved 8 December 2016.
  5. ^ a b Oun 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.
  6. ^ a b Apps 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. PMID 26113607.
  7. ^ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 513. ISBN 9783527607495. from the original on 2016-12-20.
  8. ^ 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.
  9. ^ "FOLFOX". National Cancer Institute. 18 September 2009. Retrieved 26 May 2022.
  10. ^ "CAPOX". National Cancer Institute. 4 April 2012. Retrieved 26 May 2022.
  11. ^ "XELOX". National Cancer Institute. 6 January 2012. Retrieved 26 May 2022.
  12. ^ Townsend D (2007). "Oxaliplatin". xPharm: The Comprehensive Pharmacology Reference. Elsevier. doi:10.1016/B978-008055232-3.62973-3.
  13. ^ 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.
  14. ^ 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.
  15. ^ a b Pasetto 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.
  16. ^ 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.
  17. ^ 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.
  18. ^ a b Chay 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.
  19. ^ "Oxaliplatin Side Effects". Drugs.com. from the original on 2014-09-05. Retrieved 2014-09-05.
  20. ^ "Eloxatin information". mein.sanofi.de (in German). from the original on 2016-08-27. Retrieved 2016-06-15.
  21. ^ 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.
  22. ^ Graham J, Mushin M, Kirkpatrick P (January 2004). "Oxaliplatin". Nature Reviews. Drug Discovery. 3 (1): 11–12. doi:10.1038/nrd1287. PMID 14756144.
  23. ^ 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.
  24. ^ 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.
  25. ^ "Eloxatin FDA Approval History". Drugs.com.
  26. ^ "Generic Eloxatin availability". Drugs.com. from the original on 7 June 2013. Retrieved 19 April 2014.
  27. ^ "Hospira Announces U.S. Re-Launch Of Generic Oxaliplatin Injection" (Press release). from the original on 2015-09-24. Retrieved 2015-08-25.
  28. ^ "Top 10 best-selling cancer drugs: Eloxatin–$1.2 billion". FiercePharma. 15 May 2012. from the original on 21 April 2014. Retrieved 20 April 2014.
  29. ^ a b . Orange Book. U.S. Food and Drug Administrartion. Archived from the original on 2007-09-26.. Accessed on: July 22, 2007.

Further reading edit

  • Graham J, Mushin M, Kirkpatrick P (January 2004). (PDF). Nature Reviews. Drug Discovery. 3 (1): 11–12. doi:10.1038/nrd1287. PMID 14756144. Archived from the original (PDF) on 2004-11-08. Retrieved 2005-07-19.

External links edit

  • "Oxaliplatin". Drug Information Portal. U.S. National Library of Medicine.
  • "Oxaliplatin". National Cancer Institute. 5 October 2006.

December 15, 2023
oxaliplatin, sold, under, brand, name, eloxatin, among, others, cancer, medication, platinum, based, antineoplastic, class, used, treat, colorectal, cancer, given, injection, into, vein, clinical, datatrade, nameseloxatinahfs, drugs, commonographmedlineplusa60. Oxaliplatin sold under the brand name Eloxatin among others is a cancer medication platinum based antineoplastic class used to treat colorectal cancer 4 It is given by injection into a vein 4 OxaliplatinClinical dataTrade namesEloxatinAHFS Drugs comMonographMedlinePlusa607035License dataUS DailyMed OxaliplatinRoutes ofadministrationIntravenousATC codeL01XA03 WHO Legal statusLegal statusUS WARNING 1 Rx only 2 Pharmacokinetic dataBioavailabilityCompleteElimination half life 10 25 minutes 3 ExcretionKidneyIdentifiersIUPAC name 1R 2R cyclohexane 1 2 diamine ethanedioato O O platinum II CAS Number61825 94 3 NPubChem CID77994DrugBankDB00526 NChemSpider8062727 NUNII04ZR38536JKEGGD01790 YChEMBLChEMBL414804 NPDB ligand1PT PDBe RCSB PDB CompTox Dashboard EPA DTXSID0036760ECHA InfoCard100 150 118Chemical and physical dataFormulaC 8H 14N 2O 4PtMolar mass397 294 g mol 13D model JSmol Interactive imageSMILES O1C O C O O Pt 2 12 NH2 C0CCCCC0 NH2 2 N Y what is this verify Common side effects include numbness feeling tired nausea diarrhea and low blood cell counts 4 5 Other serious side effects include allergic reactions 5 4 Use in pregnancy is known to harm the baby 4 Oxaliplatin is in the platinum based antineoplastic family of medications 6 It is believed to work by blocking the duplication of DNA 4 Oxaliplatin was patented in 1976 in Japan and approved for medical use in 1996 in Europe 7 It is on the 2023 World Health Organization s List of Essential Medicines 8 Contents 1 Medical uses 1 1 Advanced colorectal cancer 2 Adverse effects 3 Structure and mechanism 4 History 5 Patent information 6 References 7 Further reading 8 External linksMedical uses editOxaliplatin is used for treatment of colorectal cancer typically along with folinic acid leucovorin and fluorouracil in a combination known as FOLFOX 9 or along with capecitabine in a combination known as CAPOX 10 or XELOX 11 It may also be effective against breast cancer germ cell tumor ovarian cancer non small cell lung cancer and pancreatic cancer 12 Advanced colorectal cancer edit Oxaliplatin by itself has modest activity against advanced colorectal cancer 13 When compared with just 5 fluorouracil and folinic acid administered according to the de Gramont regimen a FOLFOX4 regime produced no significant increase in overall survival but did produce an improvement in progression free survival the primary end point of the phase III randomized trial 14 Adverse effects editSide effects of oxaliplatin treatment can potentially include Neurotoxicity leading to chemotherapy induced peripheral neuropathy a progressive enduring and often irreversible tingling numbness intense pain and hypersensitivity to cold beginning in the hands and feet and sometimes involving the arms and legs often with deficits in proprioception 15 This chronic neuropathy may also be preceded by a transient acute neuropathy occurring at the time of infusion and associated with excitation of voltage gated Na channels 16 17 Fatigue Nausea vomiting or diarrhea Neutropenia low number of a type of white blood cells Ototoxicity hearing loss Extravasation if oxaliplatin leaks from the infusion vein it may cause severe damage to the connective tissues Hypokalemia low blood potassium which is more common in women than men 18 Persistent hiccups 19 Rhabdomyolysis 20 In addition some patients may experience an allergic reaction to platinum containing drugs This is more common in women 18 Oxaliplatin has less ototoxicity and nephrotoxicity than cisplatin and carboplatin 15 Structure and mechanism editThe compound features a square planar platinum II center In contrast to other drugs of the platinum based antineoplastic class of drugs cisplatin and carboplatin oxaliplatin features the bidentate ligand trans 1 2 diaminocyclohexane in place of the two monodentate ammine ligands It also features a bidentate oxalate group 6 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 21 According to in vivo studies oxaliplatin fights carcinoma of the colon through non targeted cytotoxic effects Like other platinum compounds its cytotoxicity is thought to result from inhibition of DNA synthesis in cells In particular oxaliplatin forms both inter and intra strand cross links in DNA 22 which prevent DNA replication and transcription causing cell death History editOxaliplatin was first synthesized in 1978 at Nagoya City University by Yoshinori Kidani 23 It was later developed in Europe as a less toxic and more effective alternative to cisplatin It gained European approval in 1996 24 and approval by the U S Food and Drug Administration in 2002 25 Generic oxaliplatin was first approved in the United States in August 2009 26 Patent disputes caused generic production to stop in 2010 but it restarted in 2012 27 28 Patent information editEloxatin was covered by patent numbers 5338874 expired April 7 2013 5420319 expired August 8 2016 5716988 expired August 7 2015 and 5290961 expired January 12 2013 see Electronic Orange Book patent info for Eloxatin 29 Exclusivity code I 441 which expired on November 4 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 August 9 2007 29 References edit FDA sourced list of all drugs with black box warnings Use Download Full Results and View Query links nctr crs fda gov FDA Retrieved 22 Oct 2023 Eloxatin oxaliplatin injection solution concentrate DailyMed 22 October 2019 Retrieved 26 May 2022 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 a b c d e f Oxaliplatin The American Society of Health System Pharmacists Archived from the original on 21 December 2016 Retrieved 8 December 2016 a b Oun 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 a b Apps 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 PMID 26113607 Fischer J Ganellin CR 2006 Analogue based Drug Discovery John Wiley amp Sons p 513 ISBN 9783527607495 Archived from the original on 2016 12 20 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 FOLFOX National Cancer Institute 18 September 2009 Retrieved 26 May 2022 CAPOX National Cancer Institute 4 April 2012 Retrieved 26 May 2022 XELOX National Cancer Institute 6 January 2012 Retrieved 26 May 2022 Townsend D 2007 Oxaliplatin xPharm The Comprehensive Pharmacology Reference Elsevier doi 10 1016 B978 008055232 3 62973 3 Becouarn 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 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 a b Pasetto 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 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 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 a b Chay 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 Oxaliplatin Side Effects Drugs com Archived from the original on 2014 09 05 Retrieved 2014 09 05 Eloxatin information mein sanofi de in German Archived from the original on 2016 08 27 Retrieved 2016 06 15 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 Graham J Mushin M Kirkpatrick P January 2004 Oxaliplatin Nature Reviews Drug Discovery 3 1 11 12 doi 10 1038 nrd1287 PMID 14756144 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 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 Eloxatin FDA Approval History Drugs com Generic Eloxatin availability Drugs com Archived from the original on 7 June 2013 Retrieved 19 April 2014 Hospira Announces U S Re Launch Of Generic Oxaliplatin Injection Press release Archived from the original on 2015 09 24 Retrieved 2015 08 25 Top 10 best selling cancer drugs Eloxatin 1 2 billion FiercePharma 15 May 2012 Archived from the original on 21 April 2014 Retrieved 20 April 2014 a b 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 from the original on 2007 09 26 Accessed on July 22 2007 Further reading editGraham J Mushin M Kirkpatrick P January 2004 Oxaliplatin PDF Nature Reviews Drug Discovery 3 1 11 12 doi 10 1038 nrd1287 PMID 14756144 Archived from the original PDF on 2004 11 08 Retrieved 2005 07 19 External links edit Oxaliplatin Drug Information Portal U S National Library of Medicine Oxaliplatin National Cancer Institute 5 October 2006 Portal nbsp Medicine Retrieved from https en wikipedia org w index php title Oxaliplatin amp oldid 1187391524, wikipedia, wiki, book, books, library,

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