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Effects of 4,4'-Diacetyl-diphenyl-urea-bis(guanylhydrazone) on a Spectrum of Mouse and Rat Tumors¹

Department of Experimental Therapeutics, Roswell Park Memorial Institute, Buffalo, New York, and Research Laboratories of the Pharmaceutical Department, CIBA Limited, Basel, Switzerland

The antitumor action of the dihydrochloride and the dimethanesulfonate salts of 4,4'-diacetyl-diphenyl-urea-bis(guanylhydrazone) was studied in 21 mouse and rat tumors. When compared in the same test system, the 2 salts had similar activity. Marked inhibition of tumor growth and/or prolongation of host survival was noted in mice bearing leukemias L1210, P815, P388, P388/NSC 57148, P288, P1534JS and L5178Y, lymphoma AK4, Ehrlich ascites carcinoma, primary mammary tumors of the C3H and DBA/2Ha strain. No significant effect was seen in mice bearing Sarcoma 180 (tumor lines obtained from the Chester Beatty and the Sloan-Kettering Institute), adenocarcinoma 755, adenocarcinoma EO 771, and solid Ehrlich carcinoma, and in rats bearing uterus epithelioma T-8 Guerin, Flexner-Jobling carcinoma, Dunning leukemia R3323, and Walker carcinosarcoma 256 (tumor lines obtained from the Chester Beatty and the Sloan-Kettering Institute). In mice bearing sensitive leukemias, maximum therapeutic activity was noted when both tumor cells and drug were inoculated i.p. Substantial effects were also obtained, however, when the leukemic cells were inoculated s.c. or i.m. and treatment was given i.p. The results of this study indicate that, in mice, 4,4'-diacetyl-diphenyl-urea-bis(guanylhydrazone) is a potent antileukemic agent which also has inhibitory activity against autochthonous mammary tumors.

¹ This investigation was supported in part by a research grant (CA-04130) from the National Cancer Institute, USPHS.

² Present address: Research Laboratories, CIBA, Summit, New Jersey.

Received 6/16/67. Accepted 11/19/67.