Platinum preparations are cytostatic antitumor chemotherapeutic drugs of the alkylating type, containing divalent platinum (II) in the composition of the molecules and are informally referred to simply as “platinum”. All of these drugs are coordination complexes of divalent platinum.
Content
Platinum toxicity
A serious dose-limiting toxic effect in the treatment of malignant tumors with the help of platinum preparations is their high neurotoxicity, leading to the development of peripheral neuropathies, including polyneuropathies. It is important to keep in mind their high ototoxicity, leading to the development of deafness , nephrotoxicity , leading to the development of renal failure and hematotoxicity, leading to severe immunosuppression , the development of leukopenia , thrombocytopenia and anemia . Also, platinum preparations have a very high emetogenicity . [one]
Mechanism of Action
The mechanism of action of cisplatin is best studied. However, there is reason to believe that the mechanism of action of other antitumor preparations of platinum does not differ or differs slightly. Platinum derivatives, like the classic alkylating antitumor drugs , cause various damages to the DNA of malignant cells - monoadducts, interchain cross-links, intrachain cross-links, DNA cross-links with protein molecules . Platinum preparations mainly affect the region of the 7th nitrogen atom in the guanine nucleotide bases , forming [1, 2] an intrachain cross-link. [2] [3]
The cross-linking resulting from the effects of platinum preparations inhibits the possibility of repairing DNA damage by specialized enzymes , and also eliminates the possibility of “unfolding" the DNA double helix, “unwinding” the chains and the synthesis of new DNA, which is necessary for the implementation of the process of cell division ( mitosis ). As a result, a malignant cell that has lost the ability to divide undergoes apoptosis .
Platinum preparations are sometimes referred to as “non-classical alkylating preparations”, sometimes they are referred to as “alkyl-like” preparations, due to the similarity of their effects at the cellular level and their mechanism of action with the effects and mechanism of action of “classical” alkylating preparations, despite the absence of platinum preparations active alkyl groups. [four]
Examples
- Cisplatin , historically the first clinically used platinum drug. Cisplatin is especially effective against testicular malignancies ; after its introduction into clinical practice, 5-year relapse-free survival in malignant testicular tumors increased from 10% to 85% [5]
- Cis-dihydroxydiamindichloroplatin (II) ( platinum );
- Lipoplatin , an improved liposomal version of cisplatin.
- Carboplatin , a second-generation platinum antitumor drug.
- Oxaliplatin , a third-generation platinum antitumor drug.
- Cycloplatam
- Satraplatin
- Picoplatin
- Nedaplatin
- Triplatin tetranitrate
Links
- ↑ Donzelli E. , Carfì M. , Miloso M. , Strada A. , Galbiati S. , Bayssas M. , Griffon-Etienne G. , Cavaletti G. , Petruccioli MG , Tredici G. Neurotoxicity of platinum compounds: comparison of the effects of cisplatin and oxaliplatin on the human neuroblastoma cell line SH-SY5Y. (English) // Journal of neuro-oncology. - 2004. - Vol. 67, no. 1-2 . - P. 65-73. - PMID 15072449 .
- ↑ Poklar N., Pilch DS, Lippard SJ, Redding EA, Dunham SU, Breslauer KJ Influence of cisplatin intrastrand crosslinking on the conformation, thermal stability, and energetics of a 20-mer DNA duplex (Eng.) // Proceedings of the National Academy of Sciences of the United States of America : journal. - 1996 .-- July ( vol. 93 , no. 15 ). - P. 7606-7611 . - DOI : 10.1073 / pnas.93.15.7606 . - PMID 8755522 .
- ↑ Rudd GN, Hartley JA, Souhami RL Persistence of cisplatin-induced DNA interstrand crosslinking in peripheral blood mononuclear cells from elderly and young individuals ( Cancer Chemother. Pharmacol : journal. - 1995. - Vol. 35 , no. 4 . - P. 323—326 . - DOI : 10.1007 / BF00689452 . - PMID 7828275 .
- ↑ Cruet-Hennequart S., Glynn MT, Murillo LS, Coyne S., Carty MP Enhanced DNA-PK-mediated RPA2 hyperphosphorylation in DNA polymerase eta-deficient human cells treated with cisplatin and oxaliplatin (Eng.) // DNA Repair (Amst .) : journal. - 2008 .-- April ( vol. 7 , no. 4 ). - P. 582-596 . - DOI : 10.1016 / j.dnarep.2007.12.01.01 . - PMID 18289945 .
- ↑ Einhorn LH. Treatment of testicular cancer: a new and improved model (English) // J. Clin. Oncol. : journal. - 1990. - 1 November ( vol. 8 , no. 11 ). - P. 1777-1781 . - PMID 1700077 .