Oxaliplatin

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Oxaliplatin
Oxaliplatin-2D-skeletal.svg
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Clinical data
Trade names Eloxatin
AHFS/Drugs.com Monograph
MedlinePlus a607035
License data
Routes of
administration
Intravenous
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability Complete
Elimination half-life ~10 – 25 minutes [4]
Excretion Kidney
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 InfoCard 100.150.118 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C8H14N2O4Pt
Molar mass 397.294 g·mol−1
3D model (JSmol)
  • O1C(=O)C(=O)O[Pt-2]12[NH2+]C0CCCCC0[NH2+]2
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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]

Contents

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]

Related Research Articles

<span class="mw-page-title-main">Chemotherapy</span> Treatment of cancer using drugs that inhibit cell division or kill cells

Chemotherapy is a type of cancer treatment that uses one or more anti-cancer drugs as part of a standardized chemotherapy regimen. Chemotherapy may be given with a curative intent or it may aim to prolong life or to reduce symptoms. Chemotherapy is one of the major categories of the medical discipline specifically devoted to pharmacotherapy for cancer, which is called medical oncology.

<span class="mw-page-title-main">Folinic acid</span> Derivative of folic acid used in cancer treatment

Folinic acid, also known as leucovorin, is a medication used to decrease the toxic effects of methotrexate and pyrimethamine. It is also used in combination with 5-fluorouracil to treat colorectal cancer and pancreatic cancer, may be used to treat folate deficiency that results in anemia, and methanol poisoning. It is taken by mouth, injection into a muscle, or injection into a vein.

<span class="mw-page-title-main">Carboplatin</span> Medication used to treat cancer

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<span class="mw-page-title-main">Cisplatin</span> Chemical compound and pharmaceutical drug

Cisplatin is a chemical compound with formula cis-[Pt(NH3)2Cl2]. It is a coordination complex of platinum that is used as a chemotherapy medication used to treat a number of cancers. These include testicular cancer, ovarian cancer, cervical cancer, bladder cancer, head and neck cancer, esophageal cancer, lung cancer, mesothelioma, brain tumors and neuroblastoma. It is given by injection into a vein.

<span class="mw-page-title-main">Pemetrexed</span> Chemical compound

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<span class="mw-page-title-main">Cetuximab</span> Pharmaceutical drug

Cetuximab, sold under the brand name Erbitux, is an epidermal growth factor receptor (EGFR) inhibitor medication used for the treatment of metastatic colorectal cancer and head and neck cancer. Cetuximab is a chimeric (mouse/human) monoclonal antibody given by intravenous infusion.

FOLFOX is a chemotherapy regimen for treatment of colorectal cancer, made up of the drugs folinic acid, fluorouracil, and oxaliplatin.

<span class="mw-page-title-main">Irinotecan</span> Cancer medication

Irinotecan, sold under the brand name Camptosar among others, is an anti-cancer medication used to treat colon cancer and small cell lung cancer. For colon cancer it is used either alone or with fluorouracil. For small cell lung cancer it is used with cisplatin. It is given intravenously.

<span class="mw-page-title-main">Floxuridine</span> Chemical compound

Floxuridine is an oncology drug that belongs to the class known as antimetabolites. Specifically, floxuridine is a pyrimidine analog, classified as a deoxyuridine. The drug is usually administered via an artery, and most often used in the treatment of colorectal cancer. The quality of life and survival rates of individuals that receive continuous hepatic artery infusion of floxuridine for colorectal cancer metastases is significantly higher than control groups. Floxuridine can also be prescribed for the treatment of kidney and stomach cancers. In vitro uses of floxuridine include 5-minute treatments of fluorouracil, floxuridine, and mitomycin to increase cell proliferation in Tenon's capsule fibroblasts.

<span class="mw-page-title-main">Altretamine</span> Chemical compound

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FOLFIRI is a chemotherapy regimen for treatment of colorectal cancer. It is made up of the following drugs:

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IFL is a chemotherapy regimen for treatment of certain cancers, consisting of concurrent treatment with irinotecan, leucovorin, and fluorouracil.

<span class="mw-page-title-main">Satraplatin</span> Chemical compound

Satraplatin is a platinum-based antineoplastic agent that was under investigation as a treatment of patients with advanced prostate cancer who have failed previous chemotherapy. It has not yet received approval from the U.S. Food and Drug Administration. First mentioned in the medical literature in 1993, satraplatin is the first orally active platinum-based chemotherapeutic drug; other available platinum analogues—cisplatin, carboplatin, and oxaliplatin—must be given intravenously.

Aflibercept, sold under the brand names Eylea among others, is a medication used to treat wet macular degeneration and metastatic colorectal cancer. It was developed by Regeneron Pharmaceuticals and is approved in the United States and the European Union.

Platinum-based antineoplastic drugs are chemotherapeutic agents used to treat cancer. Their active moieties are coordination complexes of platinum. These drugs are used to treat almost half of people receiving chemotherapy for cancer. In this form of chemotherapy, commonly used drugs include cisplatin, oxaliplatin, and carboplatin, but several have been proposed or are under development. Addition of platinum-based chemotherapy drugs to chemoradiation in women with early cervical cancer seems to improve survival and reduce risk of recurrence.

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<span class="mw-page-title-main">Lobaplatin</span> Chemical compound

Lobaplatin is a platinum-based antineoplastic metallodrug approved exclusively in China for the treatment of small cell lung cancer, inoperable metastatic breast cancer and chronic myelogenous leukaemia. The drug is a third-generation analogue of cisplatin, the first globally approved and widely used platinum-based anticancer drug.

References

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Further reading