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]
Side-effects of oxaliplatin treatment can potentially include:
Neurotoxicity leading tochemotherapy-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 inproprioception.[18] This chronic neuropathy may also be preceded by a transient acute neuropathy occurring at the time of infusion and associated with excitation ofvoltage-gated Na+ channels.[19][20]
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.
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]
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]
^abcdef"Oxaliplatin". The American Society of Health-System Pharmacists.Archived from the original on 21 December 2016. Retrieved8 December 2016.
^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.PMID29632935.
^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. Retrieved26 May 2022.
^"CAPOX".National Cancer Institute. 4 April 2012. Retrieved26 May 2022.
^"XELOX".National Cancer Institute. 6 January 2012. Retrieved26 May 2022.
^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.PMID9704726.
^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.PMID10944126.
^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.PMID16806962.
^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.ISBN978-0-323-04971-9.
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