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Particular aspects of platinum compounds used at present in cancer treatment
Bernard Desoize1, Claudie Madoulet
1Laboratoire de Biochimie et de Biologie Moléculaire, EA 3306, Faculté de Pharmacie, IFR 53, 51 rue Cognacq-Jay, Reims, France. bernard.dosoize@univ-reims.fr
Abstract:
The history of platinum in cancer treatment began 150 years ago with the first synthesis of cisplatin; but it was not used in the clinic before 30 years ago. Then 3000 derivatives were synthesised and tested, with poor successes: three other derivatives only are available today. Clearly they are not more active, but they are less toxic than cisplatin, although two, carboplatin and nedaplatin, yield a cross-resistance, while one, oxaliplatin, does not. Their mechanisms of action are similar: these four pro-drugs form adducts with DNA, impairing DNA synthesis and repair then. Their pharmacokinetics are complicated since we always measure two overlapping pharmacokinetics: those of the parent compound and of the bound platinum. Cisplatin is now recommended for few cancers, it is replaced by less-toxic carboplatin, and therefore more easily used in combination. Oxaliplatin give interesting results in a number of cancers. The official recommendation in Japan for nedaplatin is head and neck, testicular, lung, oesophageal, ovarian, and cervical cancer.