Oxaliplatin, sold under the brand name Eloxatin among others, is a cancer medication (

platinum-based antineoplastic Platinum-based antineoplastic drugs (informally called platins) are chemotherapeutic agents used to treat cancer. They are coordination complexes of platinum. These drugs are used to treat almost half of people receiving chemotherapy for cancer. ...

class) used to treat colorectal cancer. It is given by

injection into a vein Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrie ...

. Common side effects include numbness, feeling tired, nausea, diarrhea, and low blood cell counts. Other serious side effects include allergic reactions. Use in

pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ...

is known to harm the baby. Oxaliplatin is in the

family of medications. It is believed to work by blocking the duplication of DNA. Oxaliplatin was patented in 1976 and approved for medical use in 1996. It is on the World Health Organization's List of Essential Medicines.

Medical uses

Oxaliplatin is used for treatment of colorectal cancer, typically along with folinic acid (leucovorin) and

fluorouracil Fluorouracil (5-FU), sold under the brand name Adrucil among others, is a cytotoxic chemotherapy medication used to treat cancer. By intravenous injection it is used for treatment of colorectal cancer, oesophageal cancer, stomach cancer, panc ...

in a combination known as FOLFOX or along with capecitabine in a combination known as CAPOX or XELOX.

Advanced colorectal cancer

Oxaliplatin by itself has modest activity against advanced colorectal cancer. When compared with just

5-fluorouracil Fluorouracil (5-FU), sold under the brand name Adrucil among others, is a cytotoxic chemotherapy medication used to treat cancer. By intravenous injection it is used for treatment of colorectal cancer, oesophageal cancer, stomach cancer, panc ...

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.

Adjuvant treatment of colorectal cancer

After and/or before the curative resection of colorectal cancer, chemotherapy based on 5-fluorouracil and folinic acid reduces the risk of relapse.

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. 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. * Fatigue *

Nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of th ...

vomiting Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose. Vomiting can be the result of ailments like food poisoning, gastroenter ...

, or

diarrhea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin w ...

* 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 * Persistent hiccups *

Rhabdomyolysis Rhabdomyolysis (also called rhabdo) is a condition in which damaged skeletal muscle breaks down rapidly. Symptoms may include muscle pains, weakness, vomiting, and confusion. There may be tea-colored urine or an irregular heartbeat. Some of ...

In addition, some patients may experience an

allergic reaction Allergies, also known as allergic diseases, refer a number of conditions caused by the hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic derm ...

to platinum-containing drugs. This is more common in women. Oxaliplatin has less ototoxicity and nephrotoxicity than cisplatin and carboplatin.

Structure and mechanism

The compound features a

square planar The square planar molecular geometry in chemistry describes the stereochemistry (spatial arrangement of atoms) that is adopted by certain chemical compounds. As the name suggests, molecules of this geometry have their atoms positioned at the corne ...

platinum(II) center. In contrast to other drugs of the

class of drugs cisplatin and

carboplatin Carboplatin, sold under the trade name Paraplatin among others, is a chemotherapy medication used to treat a number of forms of cancer. This includes ovarian cancer, lung cancer, head and neck cancer, brain cancer, and neuroblastoma. It is used ...

, oxaliplatin features the bidentate ligand ''trans''-1,2-diaminocyclohexane in place of the two monodentate ammine

ligand In coordination chemistry, a ligand is an ion or molecule (functional group) that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's elect ...

s. It also features a bidentate oxalate group. 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. According to ''

in vivo Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, and p ...

'' studies, oxaliplatin fights

carcinoma Carcinoma is a malignancy that develops from epithelial cells. Specifically, a carcinoma is a cancer that begins in a tissue that lines the inner or outer surfaces of the body, and that arises from cells originating in the endodermal, mesoderm ...

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, which prevent DNA replication and transcription, causing cell death.

History

Oxaliplatin was discovered in 1976 at

Nagoya City University , abbreviated to , is a public university in Japan. The main campus (Kawasumi) is located in Mizuho-ku, Nagoya City. Other three campuses (Yamanohata, Tanabe-dori and Kita Chikusa) are also located in the city. Nagoya City University has been r ...

by Professor Yoshinori Kidani, who was granted U.S. Patent 4,169,846 in 1979. Oxaliplatin was subsequently in-licensed by Debiopharm and developed as an advanced colorectal cancer treatment. Debiopharm licensed the drug to Sanofi-Aventis in 1994. It gained European approval in 1996 (initially in France) and approval by the U.S. Food and Drug Administration in 2002.

Generic Generic or generics may refer to: In business * Generic term, a common name used for a range or class of similar things not protected by trademark * Generic brand, a brand for a product that does not have an associated brand or trademark, other ...

oxaliplatin was first approved in the United States in August 2009. Patent disputes caused generic production to stop in 2010, but it restarted in 2012.

Patent information

Eloxatin was covered by patent numbers 5338874 (expired Apr 07, 2013), 5420319 (expired Aug 08, 2016), 5716988 (expired Aug 07, 2015) and 5290961 (expired Jan 12, 2013) (see Electronic Orange Book patent info for Eloxatin).Orange Book. accessdata.fda.gov. URL
http://www.accessdata.fda.gov/scripts/cder/ob/docs/patexclnew.cfm?Appl_No=021759&Product_No=001&table1=OB_Rx
. Accessed on: July 22, 2007. Exclusivity code I-441, which expired on Nov 04, 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 Aug 09, 2007.

References

External links

* * {{Portal bar, Medicine Coordination complexes Platinum(II) compounds Ammine complexes Oxalato complexes Platinum-based antineoplastic agents World Health Organization essential medicines Wikipedia medicine articles ready to translate Sanofi