Systematic (IUPAC) name
Clinical data
Trade names Platinol
AHFS/ monograph
MedlinePlus a684036
  • US: D (Evidence of risk)
Pharmacokinetic data
Bioavailability complete
Protein binding > 95%
Half-life 30-100 hours
Excretion Renal
15663-27-1 7pxY
PubChem CID 84691
DrugBank DB00515 7pxY
ChemSpider 76401 7pxN
UNII Q20Q21Q62J 7pxY
KEGG D00275 7pxY
ChEBI CHEBI:27899 7pxY
ChEMBL CHEMBL2068237 7pxN
Chemical data
Formula H6Cl2N2Pt
300.01 g/mol
 14pxN (what is this?)  (verify)

Cisplatin, cisplatinum, platamin, neoplatin, cismaplat[1] or cis-diamminedichloroplatinum(II)[2] (CDDP) is a chemotherapy drug. It was the first member of a class of platinum-containing anti-cancer drugs, which now also includes carboplatin and oxaliplatin. These platinum complexes react in vivo, binding to and causing crosslinking of DNA, which ultimately triggers apoptosis (programmed cell death).

It is on the World Health Organization's List of Essential Medicines, a list of the most important medications needed in a basic health system.[3]

Medical use

Cisplatin is administered intravenously as short-term infusion in normal saline for treatment of solid malignancies. It is used to treat various types of cancers, including sarcomas, some carcinomas (e.g. small cell lung cancer, and ovarian cancer), lymphomas, bladder cancer, cervical cancer,[4] and germ cell tumors. It is used in combinations with bleomycin and vinblastine in testicular cancer.[5]

Cisplatin is particularly effective against testicular cancer; the cure rate was improved from 10% to 85%.[6]

In addition, cisplatin is used in Auger therapy.

Side effects

Cisplatin has a number of side-effects that can limit its use:

  • Nephrotoxicity (kidney damage) is a major concern. The dose is reduced when the patient's creatinine clearance (a measure of renal function) is reduced. Adequate hydration and diuresis is used to prevent renal damage. The nephrotoxicity of platinum-class drugs seems to be related to reactive oxygen species and in animal models can be ameliorated by free radical scavenging agents (e.g., amifostine). Nephrotoxicity is a dose-limiting side effect.[7]
  • Neurotoxicity (nerve damage) can be anticipated by performing nerve conduction studies before and after treatment. Common neurological side effects of cisplatin include visual perception and hearing disorder, which can occur soon after treatment begins.[8] While triggering apoptosis through interfering with DNA replication remains the primary mechanism of cisplatin, this has not been found to contribute to neurological side effects. Recent studies have shown that cisplatin noncompetitively inhibits an archetypal, membrane-bound mechanosensitive sodium-hydrogen ion transporter known as NHE-1.[8] It is primarily found on cells of the peripheral nervous system, which are aggregated in large numbers near the ocular and aural stimuli-receiving centers. This noncompetitive interaction has been linked to hydroelectrolytic imbalances and cytoskeleton alterations, both of which have been confirmed in vitro and in vivo. However, NHE-1 inhibition has been found to be both dose-dependent (half-inhibition = 30 µg/mL) and reversible.[8]
  • Nausea and vomiting: cisplatin is one of the most emetogenic chemotherapy agents, but this symptom is managed with prophylactic antiemetics (ondansetron, granisetron, etc.) in combination with corticosteroids. Aprepitant combined with ondansetron and dexamethasone has been shown to be better for highly emetogenic chemotherapy than just ondansetron and dexamethasone.
  • Ototoxicity (hearing loss): there is at present no effective treatment to prevent this side effect, which may be severe. Audiometric analysis may be necessary to assess the severity of ototoxicity. Other drugs (such as the aminoglycoside antibiotic class) may also cause ototoxicity, and the administration of this class of antibiotics in patients receiving cisplatin is generally avoided. The ototoxicity of both the aminoglycosides and cisplatin may be related to their ability to bind to melanin in the stria vascularis of the inner ear or the generation of reactive oxygen species.
  • Electrolyte disturbance: Cisplatin can cause hypomagnesaemia, hypokalaemia and hypocalcaemia. The hypocalcaemia seems to occur in those with low serum magnesium secondary to cisplatin, so it is not primarily due to the cisplatin.
  • Myelotoxicity: This agent can also cause profound bone marrow suppression.[9]
  • Hemolytic anemia can be developed after several courses of cisplatin. It is suggested that an antibody reacting with a cisplatin-red-cell membrane is responsible for hemolysis.[10]

Mechanism of action

Following administration, one of the chloride ligands is slowly displaced by water (an aqua ligand), in a process termed aquation[11] . The aqua ligand in the resulting [PtCl(H2O)(NH3)2]+ is itself easily displaced, allowing the platinum atom to bind to bases. Of the bases on DNA, guanine is preferred. Subsequent to formation of [PtCl(guanine-DNA)(NH3)2]+, crosslinking can occur via displacement of the other chloride ligand, typically by another guanine.[12] Cisplatin crosslinks DNA in several different ways, interfering with cell division by mitosis. The damaged DNA elicits DNA repair mechanisms, which in turn activate apoptosis when repair proves impossible. In 2008, researchers were able to show that the apoptosis induced by cisplatin on human colon cancer cells depends on the mitochondrial serine-protease Omi/Htra2.[13] Since this was only demonstrated for colon carcinoma cells, it remains an open question if the Omi/Htra2 protein participates in the cisplatin-induced apoptosis in carcinomas from other tissues.

Most notable among the changes in DNA are the 1,2-intrastrand cross-links with purine bases. These include 1,2-intrastrand d(GpG) adducts which form nearly 90% of the adducts and the less common 1,2-intrastrand d(ApG) adducts. 1,3-intrastrand d(GpXpG) adducts occur but are readily excised by the nucleotide excision repair (NER). Other adducts include inter-strand crosslinks and nonfunctional adducts that have been postulated to contribute to cisplatin's activity. Interaction with cellular proteins, particularly HMG domain proteins, has also been advanced as a mechanism of interfering with mitosis, although this is probably not its primary method of action.

Note that although cisplatin is frequently designated as an alkylating agent, it has no alkyl group and so cannot carry out alkylating reactions. It is correctly classified as alkylating-like.

Cisplatin resistance

Cisplatin combination chemotherapy is the cornerstone of treatment of many cancers. Initial platinum responsiveness is high but the majority of cancer patients will eventually relapse with cisplatin-resistant disease. Many mechanisms of cisplatin resistance have been proposed including changes in cellular uptake and efflux of the drug, increased detoxification of the drug, inhibition of apoptosis and increased DNA repair.[14] Oxaliplatin is active in highly cisplatin-resistant cancer cells in the laboratory; however, there is little evidence for its activity in the clinical treatment of patients with cisplatin-resistant cancer.[14] The drug paclitaxel may be useful in the treatment of cisplatin-resistant cancer; the mechanism for this activity is unknown.[15]


Transplatin, the trans stereoisomer of cisplatin, has formula trans-[PtCl2(NH3)2] and does not exhibit a comparably useful pharmacological effect. Its low activity is generally thought to be due to rapid deactivation of the drug before it can arrive at the DNA.[citation needed] It is toxic, and it is desirable to test batches of cisplatin for the absence of the trans isomer. In a procedure by Woollins et al., which is based on the classic 'Kurnakov test', thiourea reacts with the sample to give derivatives which can easily be separated and detected by HPLC.[16]


The compound cis-[Pt(NH3)2(Cl)2] was first described by Michele Peyrone in 1845, and known for a long time as Peyrone's salt.[17] The structure was deduced by Alfred Werner in 1893.[12] In 1965, Barnett Rosenberg, van Camp et al. of Michigan State University discovered that electrolysis of platinum electrodes generated a soluble platinum complex which inhibited binary fission in Escherichia coli (E. coli) bacteria. Although bacterial cell growth continued, cell division was arrested, the bacteria growing as filaments up to 300 times their normal length.[18] The octahedral Pt(IV) complex cis[PtCl4(NH3)2], but not the trans isomer, was found to be effective at forcing filamentous growth of E. coli cells. The square planar Pt(II) complex, cis-[PtCl2(NH3)2] turned out to be even more effective at forcing filamentous growth.[19][20] This finding led to the observation that cis-[PtCl2(NH3)2] was indeed highly effective at regressing the mass of sarcomas in rats.[21] Confirmation of this discovery, and extension of testing to other tumour cell lines launched the medicinal applications of cisplatin. Cisplatin was approved for use in testicular and ovarian cancers by the U.S. Food and Drug Administration on 19 December 1978.,[12][22][23] and in the UK (and in several other European countries) in 1979.[24]

See also


  1. ^ Anonymous. Substance Details-Cisplatin. (accessed November 13, 2014)
  2. ^ See also metal amine complex
  3. ^ "" (PDF). 
  4. ^ National Cancer Institute. Cisplatin. (accessed November 13, 2014)
  5. ^ Praveen D, Ranadheer Chowdary P (2013). "A review on the use of Bleomycin-Cisplatin-Vinblastine combinations in therapy of testicular cancer". Indian Journal of Research in Pharmacy and Biotechnology 1 (6): 793–796. 
  6. ^ Einhorn LH (1 November 1990). "Treatment of testicular cancer: a new and improved model". J. Clin. Oncol. 8 (11): 1777–81. PMID 1700077. 
  7. ^ Loehrer PJ, Einhorn LH (May 1984). "Drugs five years later. Cisplatin". Annals of Internal Medicine 100 (5): 704–13. PMID 6370067. 
  8. ^ a b c Milosavljevic N, Duranton C, Djerbi N, Puech PH, Gounon P, Lagadic-Gossmann D et al. (2010). "Nongenomic effects of cisplatin: acute inhibition of mechanosensitive transporters and channels without actin remodeling". Cancer Res. 70 (19): 7514–22. PMID 20841472. doi:10.1158/0008-5472.CAN-10-1253. /releases/2010/10/101005141117.htm Lay summaryScienceDaily. 
  9. ^ Windsor RE, Strauss SJ, Kallis C, Wood NE, Whelan JS (April 2012). "Germline genetic polymorphisms may influence chemotherapy response and disease outcome in osteosarcoma: A pilot study". Cancer 118 (7): 1856–67. PMID 21887680. doi:10.1002/cncr.26472. 
  10. ^ Levi JA, Aroney RS, Dalley DN (June 1981). "Haemolytic anaemia after cisplatin treatment". Br Med J (Clin Res Ed) 282 (6281): 2003–4. PMC 1505958. PMID 6788166. doi:10.1136/bmj.282.6281.2003. 
  11. ^ Wang, Dong; Lippard, Stephen J. (2005). "Cellular processing of platinum anticancer drugs". Nature Reviews Drug Discovery 4 (4): 307–320. ISSN 1474-1776. doi:10.1038/nrd1691. 
  12. ^ a b c Stephen Trzaska (20 June 2005). "Cisplatin". C&EN News 83 (25). 
  13. ^ Pruefer FG, Lizarraga F, Maldonado V, Melendez-Zajgla J (June 2008). "Participation of Omi Htra2 serine-protease activity in the apoptosis induced by cisplatin on SW480 colon cancer cells". J Chemother 20 (3): 348–54. PMID 18606591. doi:10.1179/joc.2008.20.3.348. 
  14. ^ a b Stordal B, Davey M (November 2007). "Understanding cisplatin resistance using cellular models". IUBMB Life 59 (11): 696–9. PMID 17885832. doi:10.1080/15216540701636287. 
  15. ^ Stordal B, Pavlakis N, Davey R (December 2007). "A systematic review of platinum and taxane resistance from bench to clinic: an inverse relationship". Cancer Treat. Rev. 33 (8): 688–703. PMID 17881133. doi:10.1016/j.ctrv.2007.07.013. 
  16. ^ Woollins JD, Woollins A, Rosenberg B (1983). "The detection of trace amounts of trans-Pt(NH3)2Cl2 in the presence of cis-Pt(NH3)2Cl2. A high performance liquid chromatographic application of kurnakow's test". Polyhedron 2 (3): 175–178. doi:10.1016/S0277-5387(00)83954-6. 
  17. ^ Peyrone M (1844). "Ueber die Einwirkung des Ammoniaks auf Platinchlorür". Ann Chemie Pharm 51 (1): 1–29. doi:10.1002/jlac.18440510102. 
  18. ^ Rosenberg B, Vancamp L, Krigas T (1965). "Inhibition of cell division in Escherichia coli by electrolysis products from a platinum electrode". Nature 205 (4972): 698–699. PMID 14287410. doi:10.1038/205698a0. 
  19. ^ Rosenberg B, Van Camp L, Grimley EB, Thomson AJ (March 1967). "The inhibition of growth or cell division in Escherichia coli by different ionic species of platinum(IV) complexes". J. Biol. Chem. 242 (6): 1347–52. PMID 5337590. 
  20. ^ Thomson AJ (2007). Christie DA, Tansey EM, ed. "The Discovery, Use and Impact of Platinum Salts as Chemotherapy Agent for Cancer". Wellcome Trust Witnesses to Twentieth Century Medicine 30: 6–15. ISBN 978-0-85484-112-7. 
  21. ^ Rosenberg B, VanCamp L, Trosko JE, Mansour VH (April 1969). "Platinum compounds: a new class of potent antitumour agents". Nature 222 (5191): 385–6. PMID 5782119. doi:10.1038/222385a0. 
  22. ^ Carpenter DP (2010). Reputation and power: organizational image and pharmaceutical regulation at the FDA. Princeton, N.J: Princeton University Press. ISBN 0-691-14180-0. 
  23. ^ "Approval Summary for cisplatin for Metastatic ovarian tumors". FDA Oncology Tools. Food and Drug Administration, Center for Drug Evaluation and Research. 19 December 1978. Archived from the original on 8 February 2008. Retrieved 2009-07-15. 
  24. ^ Wiltshaw E (1979). "Cisplatin in the treatment of cancer". Platinum Metals Review 23 (3): 90–8. 

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