COMPARATIVE INVESTIGATION OF THE ANTITUMOR ACTIVITY OF R-74 AND CYCLOPHOSPHAMIDE

Abstract

R-74, 1, 4-di (2-methyl sulphonyloxy-ethylamino) -1, 4-dideoxyerythrite-dimethylsulphonate, is an alkylating agent whose antitumor properties were originally determined by tests against transplanted tumors. In the present study attention has been focused primarily to compare the antitumor effect between R-74 and typical alkylating agent cyclophosphamide (CTX). Mouse leukemia P-388 and L-1210, EHRLICH ascites carcinoma, sarcoma-180 and NF sarcoma solid tumor, responded to treatment with R-74, and some schedule dependency was observed. R-74 was intraperitonealy injected every day for 10 days from 24 hours after the intraperitonealy injection of leukemia P-388 into CDF1 mice, all treated animals survived more than 60 days at a dose of 10 mg/kg/day. CTX was most effective on leukemia P-388 with a dose of 27. 6 mg/kg producing an increase in median survival time of >400%, and 4 out of 7 mice survived over 60 days. The effects of R-74 on leukemia L-1210 and EHRLICH ascites carcinoma were almost equally effective with that of CTX. The effects of three therapeutic schedules (daily for 7 days, daily for 4 days, and every other day for 7 days) with R-74 were evaluated on mouse leukemia L-1210 and P-388. It was found that daily treatment for 4 days was most effective against leukemia P-388, but no remarkable schedule dependency was observed on leukemia L-1210. R-74 was intraperitonealy injected every day for 7 days from 24 hours after the subcutaneous transplantation of small piece of sarcoma-180 or NF sarcoma solid tumor by a trocar, and the agent was found to be equally effective in the treatment of sarcoma-180 and NF sarcoma solid tumor. The toxicities of R-74 were evaluated by comparing the weight of spleen and thymus between treated and untreated mice. It was observed that the weights were decreased according to the increasing of dosage. Thus, R-74 was equally or more effective with CTX but lymphatic toxicities must be considered.