Platinum-based antineoplasticdrugs (informally called platins) 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.[1] Addition of platinum-based chemotherapy drugs to chemoradiation in women with early
cervical cancer seems to improve survival and reduce risk of recurrence.[2]
As studied mainly on cisplatin, but presumably for other members as well, platinum-based antineoplastic agents cause
crosslinking of DNA as monoadduct, interstrand crosslinks, intrastrand crosslinks or DNA protein crosslinks. Mostly they act on the adjacent N-7 position of
guanine, forming a 1, 2 intrastrand crosslink.[4][5] The resultant crosslinking inhibits
DNA repair and/or
DNA synthesis. This mechanism leads to specific patterns of damage in DNA, which can kill cancer cells but can also increase the risk of
secondary tumors developing.[6]
Platinum-based antineoplastic agents are sometimes described as "alkylating-like" due to similar effects as
alkylating antineoplastic agents, although they do not have an
alkyl group.[7]
Examples
Strategies for improving platinum-based anticancer drugs usually involve changes in the neutral
spectator ligands, changes in the nature of the anions (halides vs various carboxylates), or changes in the oxidation state of the metal (Pt(II) vs Pt(IV)).
Nanotechnology has been explored to deliver platinum more efficiently in the case of
lipoplatin, which is introduced into the tumor sites thereby reducing the chance of toxicity.[8]
Cisplatin was the first to be developed.[9]Cisplatin is particularly effective against
testicular cancer; the cure rate was improved from 10% to 85%.[10] Similarly, the addition of cisplatin to adjuvant chemotherapy led to a marked increase in disease-free survival rates for patients with
medulloblastoma - again, up to around 85%. [11] This application of cisplatin was developed by pediatric oncologist Roger Packer in the early 1980s. [12]
^Oun R, Moussa YE, Wheate NJ (2018). "The side effects of platinum-based chemotherapy drugs: a review for chemists". Dalton Transactions. 47 (19): 6645–6653.
doi:
10.1039/c8dt00838h.
PMID29632935.
^Rudd GN, Hartley JA, Souhami RL (1995). "Persistence of cisplatin-induced DNA interstrand crosslinking in peripheral blood mononuclear cells from elderly and young individuals". Cancer Chemother. Pharmacol. 35 (4): 323–6.
doi:
10.1007/BF00689452.
PMID7828275.
S2CID24036376.