Clinical development of platinum complexes in cancer therapy: an historical perspective and an update.

The vast amount of basic research on platinum coordination complexes has produced, over the past 25 years, several thousand new molecules for preclinical screening and 28 compounds which have entered clinical development. The goals of these research activities have been to identify compounds with superior efficacy, reduced toxicity, lack of cross-resistance or improved pharmacological characteristics as compared with the parent compound, cisplatin. After the remarkable therapeutic effects of cisplatin had been established, only a few other platinum compounds succeeded in reaching general availability. Whereas carboplatin is an analogue with an improved therapeutic index (mostly driven by reduced organ toxicity) over that of cisplatin, new compounds clearly more active than or non-cross-resistant with cisplatin have not yet been identified. The platinum analogues that remain under investigation are focusing on expanding the utilisation of platinum therapy to tumour types not usually treated with, or responsive to, cisplatin or carboplatin. In addition, novel routes of administration constitute another avenue of research. The clinical development of platinum coordination complexes, with emphasis on those compounds still under active development, is reviewed.