Inhibition of transformation by levodopa-carbidopa in lymphocytes derived from patients with melanoma.

Levodopa-carbidopa has been widely used in the treatment of Parkinson's disease. We are currently investigating the effectiveness of this combination for the treatment of patients with advanced malignant melanoma. As part of this study, we have examined the effects of this combination on the phytohemagglutinin-induced transformation of human lymphocytes, isolated from patients with malignant melanoma prior to undergoing treatment. Levodopa, as well as carbidopa and 3 additional levodopa synthetic analogs, inhibited the transformation of phytohemagglutinin-stimulated DNA synthesis at pharmacologically attainable levels. These results confirm our earlier preclinical observations suggesting that catechols have profound intracellular metabolic effects in a variety of cells other than melanoma cells. It is possible that some of the effects of catechols in other diseases might also be mediated by similar intracellular metabolic effects, and effects on human melanoma might be mediated in part through effects on the immune system. We are currently awaiting introduction of synthetic catechols, including 3,4-dihydroxybenzylamine (NSC 263475), to extend these observations to our clinical studies in patients with advanced metastatic disease.