COMPLEXES OF METALS OTHER THAN PLATINUM AS ANTITUMOR AGENTS

The earliest reports on the therapeutic use of metals or metal-contain ing compounds in cancer and leukemia date from the sixteenth and ninet eenth centuries. They were forgotten until the 1960 s, when the antitu mour activity of the inorganic complex cis-diamminedichloroplatinum(II ) (cisplatin) was discovered. This led to the development of other typ es of non-organic cytostatic drugs. Cisplatin has developed into one o f the most frequently used and most effective cytostatic drugs for the treatment of solid carcinomas. Numerous other metal compounds contain ing platinum, other platinum metals, and even non-platinum metals were then shown to be effective against tumours in man and experimental tu mours in animals. These compounds comprise main-group metallic compoun ds of gallium, germanium, tin, and bismuth, early-transition metal com plexes of titanium, vanadium, niobium, molybdenum, and rhenium, and la te-transition metal complexes of ruthenium, rhodium, iridium, platinum , copper, and gold. Several platinum complexes and four non-platinum-m etal antitumour agents have so far entered early clinical trials. Gall ium trinitrate and spirogermanium have already passed phase II clinica l studies and have shown limited cytostatic activity against certain h uman carcinomas and lymphomas. The two early-transition metal complexe s budotitane and titanocene dichloride have just reached the end of ph ase I clinical trials and have been found to have an unusual pattern o f organ toxicity in man. Titanocene dichloride will soon enter phase I I clinical studies.