Modulation of cancer chemotherapy

Abstract

A common characteristic of most chemotherapeutic drugs is their low therapeutic ratio. Accordingly, supplementary agents which hold the promise of improving the ratio, by either reducing the toxicity of the chemotherapeutic drug towards normal tissue or increasing its toxicity towards neoplastic tissue, are the focus of considerable interest. Animal studies render it clear that, under appropriate circumstances, diethyldithiocarbamate (DSH) can protect normal tissues from the toxic effects of a variety of chemotherapeutic drugs. Moreover, DSH achieves this without compromising the tumoricidal effectiveness of the drugs in question. Additionally, such studies indicate that both DSH and disulfiram (DSSD) have the ability to increase the toxicity of some chemotherapeutic agents towards neoplastic tissue while either not affecting or reducing their toxicity towards normal tissue. Some of the advantages and benefits observed in animals have proved transferable to the clinical situation. The conditions under which other benefits of such therapy accrue have not been sufficiently clearly defined in animal studies and identifying these conditions clinically is proving difficult.