Cisplatin clinical pharmacology

In this chapter we will provide a detailed accounting of the impact that cisplatin and carboplatin have had in the treatment of cancer. We will address the major issues that constitute opportunities to enhance this impact the emergence of drug resistance, and the approaches to platinum-refractory cancers. Finally we will describe the clinical pharmacology of these agents, through an understanding of which improved treatments are expected. 

The first report on the anticancer properties of ruthenium was published in 1976 when the Ru(III) compound /ac-[RuC13(NH3)3] (Fig. 11) was found to induce filamentous growth of Escherichia coli at concentrations comparable to those at which cisplatin generates similar effects (49). This Ru(III) complex and related compounds such as cis-[RuCl2(NH3)4]Cl illustrated the potential anticancer activity of ruthenium complexes, but insolubility prevented further pharmacological use. Since these initial studies, other Ru(III) complexes have been studied for potential anticancer activity, and two compounds, NAMI-A (50) and KP1019 (51), are currently undergoing clinical trials. Remarkably,... 

Go RS, Adjei AA. Review of the comparative pharmacology and clinical activity of cisplatin and carboplatin. 

Schilsky RL, Choi KE, Grayhack J, Grimmer D, Guamieri C, Fullem L. Phase I clinical and pharmacologic study of intra-peritoneal cisplatin and fluorouracil in patients with advanced intraabdominal cancer. J Clin Oncol 1990 8(12) 2054-61. 

The discovery of the antitumour activity of cisplatin, cw-[PtCl2(NH3)2], and its subsequent clinical development are now well documented [1, 2]. The present clinical utility of this complex and its analogues make them of great interest both from the chemical and pharmacological viewpoint. 

Bottone MG, Santin G, Piccohni VM et al (2012) Gisplatinneiuotoxicity induces cell death in vivo and in vitro. Cisplatin nemotoxicity induces cell death in vivo and in vitro. In Kojima T, Morita Y (eds) Cisplatin pharmacology. Clinical uses and adverse effects. Nova Science Publishers, Hauppauge, NY, pp 123-140... 

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