Oxaliplatin

Routes of
administrationIntravenousATC codeLegal statusLegal status Pharmacokinetic dataBioavailabilityCompleteElimination half-life~10 – 25 minutes^[4]ExcretionKidneyIdentifiersCAS NumberPubChem CIDDrugBankChemSpiderUNIIKEGGChEMBLPDB ligandCompTox Dashboard (EPA)ECHA InfoCard100.150.118 Chemical and physical dataFormulaC₈H₁₄N₂O₄PtMolar mass397.294 g·mol⁻¹3D model (JSmol) ^NY (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:

• 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.^[16] 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.^[17][18]
• 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^[19]
• Persistent hiccups^[20]
• Rhabdomyolysis^[21]

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

Further reading

External links

• "Oxaliplatin". National Cancer Institute. 5 October 2006.