Platinum Antitumour Agents

This chapter focuses on platinum antitumor agents. Biologically active platinum complexes have been under investigation for nearly two decades. The large data base on structure–activity relationships has revealed a number of principles as well as raised new questions. Mechanistically, the aquation of the compounds and their ability to cause intrastrand cross-links in defined regions of DNA appear to be the chemical events most closely associated with antitumour activity. The reaction kinetics of the compounds in aqueous systems, which may be influenced by chelate effects, steric hindrance of bulky ligands or metal oxidation state have been studied for some complexes and are amenable to reasonably precise investigation in the future. The pharmacological behavior of the complexes in animals and in humans is, however, much less well defined. Although the pharmacokinetics of a number of compounds have been studied, conclusions regarding toxic effects have only been inferred, and reasons for varying antitumour effects are even less well understood. With intense motivation, both from the oncologic and commercial communities for clinical success, attention is heavily focused on the most active compounds in terms of antitumour effects.