Particular aspects of platinum compounds used at present in cancer treatment.
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.
Desoize
Bernard
B
Laboratoire de Biochimie et de Biologie Moléculaire, EA 3306, Faculté de Pharmacie, IFR 53, 51 rue Cognacq-Jay, Reims, France. bernard.dosoize@univ-reims.fr
Madoulet
Claudie
C
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D004351:Drug Resistance; D006801:Humans; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010599:Pharmacokinetics; D017671:Platinum Compounds / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D017671:Platinum Compounds