Journal
CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY
Volume 42, Issue 3, Pages 317-325Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/S1040-8428(01)00219-0
Keywords
anticancer drugs; resistance; cisplatin; carboplatin; oxaliplatin; nedaplatin
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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. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.
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