Discovery of Improved Platinum Analogues

  • Kenneth R. Harrap
Conference paper
Part of the ESO Monographs book series (ESO MONOGRAPHS)


Although dichlorodiammine platinum II (Fig. 1) was first synthesised by Peyrone in 1845, the powerful antitumour properties (confined to the cis-isomer) remained unknown until the work of Barnett Rosenberg, some 125 years later. Rosenberg attributed the toxic effects of an alternating electric field applied to a suspension of E coli to the generation of cis-dichlorodi-ammine platinum II (cisplatin). Subsequently, cisplatin was shown to possess potent activity, both alone and in combination, against a wide spectrum of transplantable rodent tumours [see 1–3 for reviews]. Preclinical toxicology was assessed in mice, rats, guinea pigs, dogs and monkeys and the results predicted well for those toxicities subsequently found in man [4]. Nephrotoxicity was the major dose-limiting side effect in all species, accompanied by gastrointestinal, haematological and ototoxicities, together with severe emesis in dogs and monkeys [5-11].


Antitumour Activity Platinum Complex Human Ovarian Carcinoma Cell Line Metal Coordination Compound Platinum Coordination Complex 
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Copyright information

© Springer-Verlag Berlin Heidelberg 1994

Authors and Affiliations

  • Kenneth R. Harrap
    • 1
  1. 1.Drug Development SectionThe Institute of Cancer Research: Royal Cancer HospitalSuttonUK

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