Anticancer activity of new nitrosoureas against Walder carcinosarcoma 256 and DMBA-induced mammary cancer of the rat.

Three new nitrosoureas and chlorozotocin were screened for anticancer activity against Walker carcinoma 256 and DMBA-induced mammary cancer of the rat. High single doses (80% of LD50) of water-soluble 1-(2-chloroethyl)-1-nitroso-3-(methylencarboxamido)urea and 2-[3-(2-chloroethyl)-3-nitrosoureido]ethylmethansulfonate effected a similar tumor weight inhibition than BCNU in treatment of subcutaneously implanted Walker 256. In dose-response studies low doses of the new analogs effected a higher tumor weight inhibition than BCNU in the treatment of subcutaneously implanted Walker 256. The therapeutic index calculated as LD50/ED50, was 2.7 and 2.4 for the new compounds in comparison to BCNU with 2.1. Chlorozotocin and 1-(methylenecarboxyethyl)-1-nitroso-3-phenylurea were not active. Against DMBA-induced mammary cancer the new BCNU analogs yielded a greater tumor weight inhibition than adriamycin and BCNU. At a dose-level of approximately LD10, the remission rates of individual tumors, which were at least 0.6 g at the beginning of treatment were 46% (13/28) for therapy with 2-[3-(2-chloroethyl)-3-nitrosoureido]ethylmethanesulfonate, 32% (9/28) for 1-(2-chloroethyl)-1-nitro-3-(methylenecarboxamido)urea, 26% (6/23) for chlorozotocin, 21% (7/33) for adriamycin and 17% for BCNU, respectively. As single agents the 2 new analogs 2[3-(1-chloroethyl)-3-nitrossureido[ethylmethanesulfonate, the water-soluble 1-(2-chloroethyl)-1-nitroso-3-(methylenecarboxamido)urea and chlorozotocin were the most effective compounds against DMBA-induced mammary cancer of the rat.