Oxaliplatin

Last updated

Oxaliplatin
Oxaliplatin-2D-skeletal.svg
Oxaliplatin-from-xtal-Mercury-3D-balls.png
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
 X mark.svgNYes check.svgY  (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]

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

Carboplatin, sold under the brand 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 by injection into a vein.

<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

Pemetrexed, sold under the brand name Alimta among others, is a chemotherapy medication for the treatment of pleural mesothelioma and non-small cell lung cancer (NSCLC)..

<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

Altretamine, also called hexamethylmelamine, is an antineoplastic agent. It was approved by the U.S. FDA in 1990.

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

Triplatin tetranitrate is a platinum-based cytotoxic drug that underwent clinical trials for the treatment of human cancer. The drug acts by forming adducts with cellular DNA, preventing DNA transcription and replication, thereby inducing apoptosis. Other platinum-containing anticancer drugs include cisplatin, carboplatin, and oxaliplatin.

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.

FOLFIRINOX is a chemotherapy regimen for treatment of advanced pancreatic cancer. It is made up of the following four drugs:

Tegafur/gimeracil/oteracil, sold under the brand name Teysuno among others is a fixed-dose combination medication used for the treatment of advanced gastric cancer when used in combination with cisplatin, and also for the treatment of head and neck cancer, colorectal cancer, non–small-cell lung, breast, pancreatic, and biliary tract cancers.

FOLFOXIRI is a chemotherapy regimen for the treatment of advanced colorectal cancer. The role of FOLFOXIRI in colorectal cancer has been reviewed.

<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

  1. ↑ "Prescription medicines: registration of new generic medicines and biosimilar medicines, 2017". Therapeutic Goods Administration (TGA). 21 June 2022. Retrieved 30 March 2024.
  2. ↑ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA . Retrieved 22 October 2023.
  3. ↑ "Eloxatin- oxaliplatin injection, solution, concentrate". DailyMed. 22 October 2019. Retrieved 26 May 2022.
  4. ↑ Ehrsson H, Wallin I, Yachnin J (2002). "Pharmacokinetics of oxaliplatin in humans". Medical Oncology. 19 (4): 261–265. doi:10.1385/MO:19:4:261. PMID   12512920. S2CID   1068099.
  5. 1 2 3 4 5 6 "Oxaliplatin". The American Society of Health-System Pharmacists. Archived from the original on 21 December 2016. Retrieved 8 December 2016.
  6. 1 2 Oun 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. PMID   29632935.
  7. 1 2 Apps MG, Choi EH, Wheate NJ (August 2015). "The state-of-play and future of platinum drugs". Endocrine-Related Cancer. 22 (4): R219–R233. doi: 10.1530/ERC-15-0237 . hdl: 2123/24426 . PMID   26113607.
  8. ↑ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 513. ISBN   9783527607495. Archived from the original on 20 December 2016.
  9. ↑ 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.
  10. ↑ "FOLFOX". National Cancer Institute. 18 September 2009. Retrieved 26 May 2022.
  11. ↑ "CAPOX". National Cancer Institute. 4 April 2012. Retrieved 26 May 2022.
  12. ↑ "XELOX". National Cancer Institute. 6 January 2012. Retrieved 26 May 2022.
  13. ↑ Townsend D (2007). "Oxaliplatin". xPharm: The Comprehensive Pharmacology Reference. Elsevier. pp. 1–4. doi:10.1016/B978-008055232-3.62973-3. ISBN   9780080552323.
  14. ↑ 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. PMID   9704726.
  15. ↑ 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. PMID   10944126.
  16. 1 2 Pasetto 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. PMID   16806962.
  17. ↑ Webster RG, Brain KL, Wilson RH, Grem JL, Vincent A (December 2005). "Oxaliplatin induces hyperexcitability at motor and autonomic neuromuscular junctions through effects on voltage-gated sodium channels". British Journal of Pharmacology. 146 (7): 1027–1039. doi:10.1038/sj.bjp.0706407. PMC   1751225 . PMID   16231011.
  18. ↑ Gebremedhn EG, Shortland PJ, Mahns DA (April 2018). "The incidence of acute oxaliplatin-induced neuropathy and its impact on treatment in the first cycle: a systematic review". BMC Cancer. 18 (1): 410. doi: 10.1186/s12885-018-4185-0 . PMC   5897924 . PMID   29649985.
  19. 1 2 Chay WY, Chew L, Yeoh TT, Tan MH (May 2010). "An association between transient hypokalemia and severe acute oxaliplatin-related toxicity predominantly in women". Acta Oncologica. 49 (4): 515–517. doi: 10.3109/02841860903464015 . PMID   20092386. S2CID   33026126.
  20. ↑ "Oxaliplatin Side Effects". Drugs.com. Archived from the original on 5 September 2014. Retrieved 5 September 2014.
  21. ↑ "Eloxatin information". mein.sanofi.de (in German). Archived from the original on 27 August 2016. Retrieved 15 June 2016.
  22. ↑ Johnstone TC (January 2014). "The Crystal Structure of Oxaliplatin: A Case of Overlooked Pseudo Symmetry". Polyhedron. 67: 429–435. doi:10.1016/j.poly.2013.10.003. PMC   3885251 . PMID   24415827.
  23. ↑ Graham J, Mushin M, Kirkpatrick P (January 2004). "Oxaliplatin". Nature Reviews. Drug Discovery. 3 (1): 11–12. doi:10.1038/nrd1287. PMID   14756144.
  24. ↑ Pizarro AM, Barry NP, Sadler PJ (2013). "3.25 - Metal–DNA Coordination Complexes". Comprehensive Inorganic Chemistry II (2nd ed.). Elsevier. pp. 751–784. doi:10.1016/B978-0-08-097774-4.00330-2. ISBN   9780080965291.
  25. ↑ 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. ISBN   978-0-323-04971-9.
  26. ↑ "Eloxatin FDA Approval History". Drugs.com.
  27. ↑ "Generic Eloxatin availability". Drugs.com. Archived from the original on 7 June 2013. Retrieved 19 April 2014.
  28. ↑ "Hospira Announces U.S. Re-Launch Of Generic Oxaliplatin Injection" (Press release). Archived from the original on 24 September 2015. Retrieved 25 August 2015.
  29. ↑ "Top 10 best-selling cancer drugs: Eloxatin–$1.2 billion". FiercePharma. 15 May 2012. Archived from the original on 21 April 2014. Retrieved 20 April 2014.
  30. 1 2 "Patent and Exclusivity Search Results from query on Appl No 021759 Product 001 in the OB_Rx list". Orange Book. U.S. Food and Drug Administrartion. Archived from the original on 26 September 2007.. Accessed on: 22 July 2007.

Further reading

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.