INHIBITION OF CISPLATIN TOXICITY WITHOUT DECREASING ANTITUMOR EFFICACY - USE OF A DITHIOCARBAMATE

Objective:To demonstrate whether a dithiocarbamate derivative, N-methy l-D-glucaminedithiocarbamate, could prevent anorexia and weight loss a nd enhance survival without decreasing the antitumor efficacy of high- dose cisplatin therapy. Design: One hundred forty-two mice were random ized into groups receiving cisplatin, 5 mg/kg per day, 7.5 mg/kg per d ay, or 10 mg/kg per day for three days with or without N-methyl-D-gluc aminedithiocarbamate, 1000 mg/kg per day. Weight loss and morbidity we re examined between groups. Antitumor efficacy of cisplatin combined w ith N-methyl-D-glucaminedithiocarbamate was examined using a subcutane ous melanoma model. Setting: Institutional laboratory. Main Outcome Me asures: N-methyl-D-glucaminedithiocarbamate intervention would decreas e morbidity, weight loss, and increase survival without decreasing the antitumor efficacy of cisplatin. Results: Weight loss and morbidity w ere significantly reduced when N-methyl-D-glucaminedithiocarbamate was coadministered with cisplatin (P<.05) at all doses of cisplatin. The antitumor efficacy of high-dose cisplatin therapy (7.5 mg/kg per day a nd 10 mg/kg per day) was not significantly decreased (P>.05) at all do ses of cisplatin. Conclusion: As N-methyl-D-glucaminedithiocarbamate s eems to limit morbidity and mortality of high-dose cisplatin administr ation without decreasing its antitumor efficacy, this drug deserves fu rther investigation in the treatment of cancer.