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Platinum compoundsIn useSerendipitous observation

Cisplatin

Also known as Platinol, Platinol-AQ, cis-diamminedichloroplatinum

A platinum complex given by injection. Introduced into cancer treatment in the 1970s, its 2022 US label lists advanced testicular, ovarian and bladder cancer.

From discovery to approval

  1. 1844 · First described

    Reviews credit Michele Peyrone with first synthesising the compound in 1844, long before its medical use. Its effect on bacterial cell division was reported in 1965 by Rosenberg and colleagues, and a 1969 paper described platinum compounds as antitumour agents; a review says the tests were in mice.[2][3][4][5][6][7][8]

  2. 1971 · First use in people · 127 years after first description

    A 2022 review states that clinical trials of cisplatin began in 1971, citing a 1974 phase I report by Higby and colleagues (titled as showing responses in testicular and other tumours). A 2011 review instead says the 1978 US approval came six years after trials by the NCI and Bristol-Myers Squibb.[2]

  3. 1978-12-19 · FDA regular · 134 years after first description

    Cisplatin injection (Platinol), NDA 018057, original approval, classed as a new molecular entity with standard review in the Drugs@FDA history. The original label and letter are not available there, so the indication at approval is not stated here; the current label lists advanced testicular, ovarian and bladder cancer. The type regular is an inference: no accelerated-approval wording was found.[8]

How it works

Binds to DNA and forms cross-links within and between strands. These distort the DNA, interfere with copying and reading it, and are thought to trigger programmed cell death (apoptosis). Its geometric isomer, trans-DDP, is ineffective as a chemotherapy drug.[1]

Where it came from and why

The 1844 work was chemical: the paper's title concerns the action of ammonia on platinum chloride. The medical use arose in 1965, when Rosenberg was studying how an electric field affects Escherichia coli; the bacteria stopped dividing, and he proposed that such an agent might also stop tumour cell growth. Two reviews call the discovery serendipitous or accidental.

Cisplatin was first made in 1844 by Michele Peyrone, and its structure was worked out by Alfred Werner in 1893 [2]. Its potential as an anticancer agent was not recognised until the 1960s [2].

In 1965 Barnett Rosenberg and colleagues reported that products of electrolysis from a platinum electrode inhibited cell division in Escherichia coli [6]. One review describes the bacteria as ceasing to divide while growing about 300-fold in size [4]. Reviews differ in how they describe the work that followed, but they agree that the effect came from products formed from the platinum electrodes, and that cisplatin was identified as an active compound [2] [4] [3].

A review says Rosenberg hypothesised that a substance able to stop bacteria dividing might also stop tumour cells growing [4]. A 1969 paper reported platinum compounds as a new class of antitumour agents [7], and a review states that cisplatin reduced the mean tumour mass of sarcoma-180 and lengthened survival in mice with L1210 leukaemia [2]. Clinical trials began in 1971 according to the same review [2], and the US Food and Drug Administration approved cisplatin in 1978 [8].

Cancers

  • Testicular cancer

    Used with vinblastine and bleomycin in a 1977 series of disseminated testicular cancer; the 2022 US label lists advanced testicular cancer.[9]

  • Ovarian cancer

    Tested in 34 patients with advanced ovarian adenocarcinoma resistant to conventional chemotherapy in a 1976 phase II study; the 2022 US label lists advanced ovarian cancer.[10]

  • Bladder cancer

    The 2022 US label lists advanced bladder cancer.[11]

Family and partners

Drugs derived from it: Carboplatin, Oxaliplatin, Nedaplatin, Miriplatin, Lobaplatin, Satraplatin, Heptaplatin

Worth knowing

  • Reviews credit Michele Peyrone with first synthesising cisplatin in 1844, and Alfred Werner with determining its structure in 1893.[2]
  • In Rosenberg's 1965 experiments, a review reports that the bacteria stopped dividing but grew about 300-fold in size.[4]
  • The geometric isomer of cisplatin, trans-DDP, is ineffective as a chemotherapy drug.[1]
  • In a 1977 series of 50 patients with disseminated testicular cancer, cisplatin with vinblastine and bleomycin produced 74% complete and 26% partial remissions as reported by the authors; three patients could not be evaluated because of early death.[9]
  • The 2022 US label gives 1978 as the year of initial US approval.[11]

On this site

References

  1. Trimmer EE, Essigmann JM. Cisplatin. Essays Biochem. 1999;34:191-211. PubMedDOI
  2. Forgie BN, Prakash R, Telleria CM. Revisiting the Anti-Cancer Toxicity of Clinically Approved Platinating Derivatives. Int J Mol Sci. 2022;23(23). PubMedDOI
  3. Makovec T. Cisplatin and beyond: molecular mechanisms of action and drug resistance development in cancer chemotherapy. Radiol Oncol. 2019;53(2):148-158. PubMedDOI
  4. Monneret C. Platinum anticancer drugs. From serendipity to rational design. Ann Pharm Fr. 2011;69(6):286-95. PubMedDOI
  5. Kelland L. The resurgence of platinum-based cancer chemotherapy. Nat Rev Cancer. 2007;7(8):573-84. PubMedDOI
  6. ROSENBERG B, VANCAMP L, KRIGAS T. INHIBITION OF CELL DIVISION IN ESCHERICHIA COLI BY ELECTROLYSIS PRODUCTS FROM A PLATINUM ELECTRODE. Nature. 1965;205:698-9. PubMedDOI
  7. Rosenberg B, VanCamp L, Trosko JE, Mansour VH. Platinum compounds: a new class of potent antitumour agents. Nature. 1969;222(5191):385-6. PubMedDOI
  8. U.S. Food and Drug Administration. Drugs@FDA: Approval date(s) and history, letters, labels, reviews for NDA 018057 (cisplatin; Platinol, Platinol-AQ). Page read 2026-10-25. Source
  9. Einhorn LH, Donohue J. Cis-diamminedichloroplatinum, vinblastine, and bleomycin combination chemotherapy in disseminated testicular cancer. Ann Intern Med. 1977;87(3):293-8. PubMedDOI
  10. Wiltshaw E, Kroner T. Phase II study of cis-dichlorodiammineplatinum(II) (NSC-119875) in advanced adenocarcinoma of the ovary. Cancer Treat Rep. 1976;60(1):55-60. PubMed
  11. U.S. Food and Drug Administration. Cisplatin for injection, prescribing information (NDA 018057, supplement 092, 24 March 2022). Source
  12. Higby DJ, Wallace HJ Jr, Albert DJ, Holland JF. Diaminodichloroplatinum: a phase I study showing responses in testicular and other tumors. Cancer. 1974;33(5):1219-5. PubMedDOI