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Use of a Dithiocarbamate

Suzanne Yee, MD; Mary Fazekas-May, MD; Earnest M. Walker, MD, PhD; Donna Montague; Scott Stern, MD; Kenneth W. Heard, PhD

Arch Otolaryngol Head Neck Surg. 1994;120(11):1248-1252.

Abstract
Objective
To demonstrate whether a dithiocarbamate derivative, N-methyl-D-glucaminedithiocarbamate, could prevent anorexia and weight loss and enhance survival without decreasing the antitumor efficacy of high-dose cisplatin therapy.

Design
One hundred forty-two mice were randomized into groups receiving cisplatin, 5 mg/kg per day, 7.5 mg/kg per day, or 10 mg/kg per day for three days with or without N-methyl-D-glucaminedithiocarbamate, 1000 mg/kg per day. Weight loss and morbidity were examined between groups. Antitumor efficacy of cisplatin combined with N-methyl-D-glucaminedithiocarbamate was examined using a subcutaneous melanoma model.

Setting
Institutional laboratory.

Main Outcome Measures
N-methyl-D-glucaminedithiocarbamate intervention would decrease morbidity, weight loss, and increase survival without decreasing the antitumor efficacy of cisplatin.

Results
Weight loss and morbidity were 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 and 10 mg/kg per day) was not significantly decreased (P>.05) at all doses of cisplatin.

Conclusion
As N-methyl-D-glucaminedithiocarbamate seems to limit morbidity and mortality of high-dose cisplatin administration without decreasing its antitumor efficacy, this drug deserves further investigation in the treatment of cancer.

(Arch Otolaryngol Head Neck Surg. 1994;120:1248-1252)

Author Affiliations
From the Department of Otolaryngology, University of Arkansas for Medical Sciences, Little Rock (Drs Yee, Fazekas-May, Stern, and Heard, and Ms Montague), and the Department of Pathology, Marshall University School of Medicine, Huntington, WVa (Dr Walker).

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