Jump to content

Oxaliplatin

From Wikipedia, the free encyclopedia
The printable version is no longer supported and may have rendering errors. Please update your browser bookmarks and please use the default browser print function instead.

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[4]
ExcretionKidney
Identifiers
  • [(1R,2R)-cyclohexane-1,2-diamine](ethanedioato-O,O')platinum(II)
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
PDB ligand
CompTox Dashboard (EPA)
ECHA InfoCard100.150.118 Edit 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 name Eloxatin among others, is a cancer medication (platinum-based antineoplastic class) used to treat colorectal cancer.[5] It is given by injection into a vein.[5]

Common side effects include numbness, feeling tired, nausea, diarrhea, and low blood cell counts.[5][6] Other serious side effects include allergic reactions.[6][5] Use in pregnancy is known to harm the baby.[5] Oxaliplatin is in the platinum-based antineoplastic family of medications.[7] It is believed to work by blocking the duplication of DNA.[5]

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

Medical uses

Oxaliplatin is used for treatment of colorectal cancer, typically along with folinic acid (leucovorin) and fluorouracil in a combination known as FOLFOX[10] or along with capecitabine in a combination known as CAPOX[11] or XELOX.[12] It may also be effective against breast cancer, germ cell tumor, ovarian cancer, non-small-cell lung cancer, and pancreatic cancer.[13]

Advanced colorectal cancer

Oxaliplatin by itself has modest activity against advanced colorectal cancer.[14] 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.[15]

Adverse effects

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.[19]

Oxaliplatin has less ototoxicity and nephrotoxicity than cisplatin and carboplatin.[16]

Structure and mechanism

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.[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.[22]

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,[23] which prevent DNA replication and transcription, causing cell death.

History

Oxaliplatin was first synthesized in 1978 at Nagoya City University by Yoshinori Kidani.[24] It was later developed in Europe as a less toxic and more effective alternative to cisplatin. It gained European approval in 1996,[25] and approval by the U.S. Food and Drug Administration in 2002.[26] Generic oxaliplatin was first approved in the United States in August 2009.[27] Patent disputes caused generic production to stop in 2010, but it restarted in 2012.[28][29]

Patent information

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).[30] 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.[30]

References

  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 October 2023.
  2. ^ "Prescription medicines: registration of new generic medicines and biosimilar medicines, 2017". Therapeutic Goods Administration (TGA). 21 June 2022. Retrieved 30 March 2024.
  3. ^ "Eloxatin- oxaliplatin injection, solution, concentrate". DailyMed. 22 October 2019. Retrieved 26 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. ^ 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.
  6. ^ 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.
  7. ^ 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. 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. Retrieved 26 May 2022.
  11. ^ "CAPOX". National Cancer Institute. 4 April 2012. Retrieved 26 May 2022.
  12. ^ "XELOX". National Cancer Institute. 6 January 2012. Retrieved 26 May 2022.
  13. ^ Townsend D (2007). "Oxaliplatin". xPharm: The Comprehensive Pharmacology Reference. Elsevier. pp. 1–4. doi:10.1016/B978-008055232-3.62973-3. ISBN 9780080552323.
  14. ^ 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.
  15. ^ 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.
  16. ^ 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.
  17. ^ 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.
  18. ^ 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.
  19. ^ 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.
  20. ^ "Oxaliplatin Side Effects". Drugs.com. Archived from the original on 5 September 2014. Retrieved 5 September 2014.
  21. ^ "Eloxatin information". mein.sanofi.de (in German). Archived from the original on 27 August 2016. Retrieved 15 June 2016.
  22. ^ 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.
  23. ^ Graham J, Mushin M, Kirkpatrick P (January 2004). "Oxaliplatin". Nature Reviews. Drug Discovery. 3 (1): 11–12. doi:10.1038/nrd1287. PMID 14756144.
  24. ^ 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.
  25. ^ 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.
  26. ^ "Eloxatin FDA Approval History". Drugs.com.
  27. ^ "Generic Eloxatin availability". Drugs.com. Archived from the original on 7 June 2013. Retrieved 19 April 2014.
  28. ^ "Hospira Announces U.S. Re-Launch Of Generic Oxaliplatin Injection" (Press release). Archived from the original on 24 September 2015. Retrieved 25 August 2015.
  29. ^ "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.
  30. ^ 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 26 September 2007.. Accessed on: 22 July 2007.

Further reading

Retrieved from "https://en.wikipedia.org/enwiki/w/index.php?title=Oxaliplatin&oldid=1224338038"