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

Abstract

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.

• Authors: H H Fiebig, G Eisenbrand, W J Zeller, R Zentgraf
• Journal: Oncology (Oncology) Vol. 37 Issue 3 Pg. 177-83 ( 1980) ISSN: 0030-2414 [Print] Switzerland
• PMID: 6444708 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Antineoplastic Agents
• Nitrosourea Compounds
• acetamido-CNU
• chlorozotocin
• 9,10-Dimethyl-1,2-benzanthracene
• Streptozocin
• Carmustine

Topics

• 9,10-Dimethyl-1,2-benzanthracene
• Animals
• Antineoplastic Agents
• Bone Marrow (drug effects)
• Carcinoma 256, Walker (drug therapy)
• Carmustine (therapeutic use)
• Drug Evaluation, Preclinical
• Female
• Lethal Dose 50
• Mammary Neoplasms, Experimental (chemically induced, drug therapy)
• Nitrosourea Compounds (therapeutic use, toxicity)
• Rats
• Streptozocin (analogs & derivatives, therapeutic use)