Particular aspects of platinum compounds used at present in cancer treatment

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.