Experimental evaluation of potential anticancer agents. I. Quantitative therapeutic evaluation of certain purine analogs.

Abstract

Summary A study of the degree of reproducibility of the Carcinoma 755 system when employed to obtain therapeutic indices of purine antagonists has been carried out. Some 60 “active” purine analogs have been studied by this system, used in a quantitative manner, and the approximate LD 10 9s, minimum effective doses, therapeutic indices (LD 10 /T/C 0.10), and maximum degrees of effectiveness (T/C at the LD 10 ) of each of these compounds are recorded. Under the conditions employed, only 6-mercaptopurine ribonucleoside possessed a therapeutic index against Ca-755 which was clearly greater than that of 6-mercaptopurine, whereas several derivatives of 6-mercaptopurine possessed therapeutic indices of the same magnitude of 6-mercaptopurine. When the limited number of purine analogs which have received clinical trial against human leukemias were compared as to “useful clinical activity” and therapeutic index in the Ca-755 system, it appeared that those with higher experimental therapeutic indices were more “useful” against certain human leukemias than were those with very low therapeutic indices in the Ca-755 system.