Inhibition of cisplatin toxicity without decreasing antitumor efficacy. Use of a dithiocarbamate.
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.


METHODS
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.


METHODS
Institutional laboratory.


METHODS
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.


CONCLUSIONS
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.
Yee
S
S
Department of Otolaryngology, University of Arkansas for Medical Sciences, Little Rock.
Fazekas-May
M
M
Walker
E M
EM
Montague
D
D
Stern
S
S
Heard
K W
KW
D000818:Animals; D000855:Anorexia / Q000139:chemically induced / Q000517:prevention & control*; D001835:Body Weight / Q000187:drug effects*; D002614:Chelating Agents / Q000627:therapeutic use*; D002945:Cisplatin / Q000009:adverse effects*; D008297:Male; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000401:mortality; D051379:Mice; D008810:Mice, Inbred C57BL; D011897:Random Allocation; D013012:Sorbitol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013113:Spin Labels; D016019:Survival Analysis; D013859:Thiocarbamates / Q000627:therapeutic use*; D016896:Treatment Outcome
D002614:Chelating Agents; D013113:Spin Labels; D013859:Thiocarbamates; D013012:Sorbitol; C041262:N-methyl-D-glucamine dithiocarbamate; D002945:Cisplatin