Platinum Complexes for the Treatment of Cancer

Abstract

Some platinum coordination complexes are active anticancer drugs in animal and man. This new class of chemotherapeutics was discovered during the course of investigation of the electric field effect on bacterial growth. The platinum electrodes electrolyzed during the experiment, releasing a platinum complex which caused complete cessation of cell division in the bacterial rods. With this filamentation assay system, we were able to identify the specific chemical as cis-dichlorodiammineplatinum(II), a complex known since 1848. The bacterial studies with many such complexes suggested to us the generalizations that charged platinum complexes were bacteriocidal, while the neutral platinum complexes induced filamentation and, in lysogenic bacteria, lysis. The neutral complexes have ignificant activity against transplantable, virally induced, and chemically induced cancers in animals. They are synergistic with almost every other anticancer drug in current use. In man kidney toxicity is the dose limiting side effect but this is now completely ameliorated by simply hydrating the patient. The drug in combination therapy, has proven to be ‘potentially curable’ for all form of testicular cancer. Other cancers where the drug activity has begun to approach this are head and neck cancer, and ovarian cancer. Activity against the other major cancers is now being studied. The mechanism of action at a molecular level appear to depend upon a primary lesion formed on the cellular DNA by the platinum complex. This serendipitous discovery has led to a new class of anticancer agents, metal coordination complexes, which may prove to be of significant value.