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Evaluation of the Effect of a Pyrazolone Derivative KB-95 on the Toxicity and Activity of Some Anticancer Drugs¹

Western Institute for Cancer and Leukemia Research, Los Angeles, California

The administration of a pyrazolone compound before and after a single i.p. LD_80–100 dose of a number of anticancer drugs produced in some cases a significant reduction of the expected mortality in mice. Beneficial effects were obtained with 5-fluorouracil, azaserine, 6-mercaptopurine, and triethylenemelamine. Borderline results were obtained with actinomycin D, amethopterin, busulfan, streptonigrin, L-sarcolysin, triethylenethiophosphoramide, and vinblastine, and no effect was observed with uracil mustard and cyclophosphamide. The leukopenia and weight loss induced by the anticancer drugs were less in extent and duration in groups where the pyrazolone compound reduced the lethal effect. The pyrazolone compound given to mice with Sarcoma 180 and Ehrlich ascites tumors significantly reduced the lethal effects of treatment with nitrogen mustard without impairment of the antitumor effects of the mustard.

¹ Communication No. 13. This study was supported by grants from the following Foundations: Conrad N. Hilton, R. C. Baker, William Morris Agency, Lidow, Robert H. and Clare M. Avnet. Also the Horace E. Altfeld, Cathy Cooper, Susan Feybush, Susan Gorshow, Harold J. Rappaport, Joan Sloan Memorial Funds, International Rectifier Corporation, and the North American Aviation Employees Donate Once Club.

Received 7/23/65. Revised 11/15/65.