Platinum Co-ordination Complexes in Cancer Chemotherapy

Following its widespread adoption into clinical practice in the early 1970s the drug cispiatin (cis-diamminedichloroplatinum(II), cis[PrClfiH J2]) has improved substantially the response rate5 in a number of malignant conditions, particularly testicular and ovarian cancer. However, the clinical utility of the drug is limited by its toxic side effects. The most significant of these is kidney toxicity (nephrotoxicity), though in addition cisplatin produces severe nausea and vomiting, high frequency hearing loss and neurotoxicity. In the past decade immense efforts have been devoted to elucidating the molecular mechanism of the action of cisplatin, and its biochemistry and pharmacology, both in animals and man. Because of the toxic restrictions of the drug much attention has been devoted also to identifying analogues which retain cisplatin’s useful anti-tumour properties, but which are so far as possible devoid of its toxic limitations. The international meeting held at the University of Vermont, Burlington, U.S.A. during June 1983 provided a timely opportunity, not only to review current knowledge on the molecular mechanisms of action of platinum complexes and their pharmacological properties, but also to compare data emerging from studies of those derivatives which are undergoing clinical evaluation. Inevitably, limitations of space and the scientific predilections of this reviewer may conspire to create an unintentional imbalance in the report of what proved to be an excellently conceived and highly successful meeting. If this be so, then apologies must be accorded in advance to those scientists whose work may seem to have been overlooked. The reader is referred to Figure I for the structures of platinum complexes discussed and to the end of the article for a list of background references supporting this report. The proceedings of this conference are published by Martinus Nijhoff and full acknowledgement of the contributing authors, which is omitted from this review, can be found therein.