Oxaliplatin

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

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

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 also has uses in pancreatic cancer[12] and stomach cancer or esophageal cancer.[13] It may also be effective against breast cancer, germ cell tumor, ovarian cancer and non-small-cell lung cancer.[14]

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.[20]

Oxaliplatin has less ototoxicity and nephrotoxicity than cisplatin and carboplatin.[17]

• 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.[17] 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.[18][19]
• 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[20]
• Persistent hiccups[21]
• Rhabdomyolysis[22]

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.[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.[23]

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

History

Oxaliplatin was first synthesized in 1978 at Nagoya City University by Yoshinori Kidani.[25] It was later developed in Europe as a less toxic and more effective alternative to cisplatin. It gained European approval in 1996,[26] and approval by the U.S. Food and Drug Administration in 2002.[27] Generic oxaliplatin was first approved in the United States in August 2009.[28] Patent disputes caused generic production to stop in 2010, but it restarted in 2012.[29][30]

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).[31] 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.[31]

Further reading

External links