Evaluation of antitumor drug side effects in small animals.

This is an initial report on the development of screening tests for side effects of antitumor drugs, with small amounts of compound and short time intervals. These tests are based on acute dosing of mice and various blood or serum measurements: (a) total white blood cell count for leukopenia; (b) BUN for kidney toxicity; (c) SGPT for liver toxicity; and (d) creatine phosphokinase MB isozyme (CPK-MB) for cardiotoxicity. A correlation with the toxicity observed in other species is developed by establishing the effect of a prototype compound for each toxicity and tests of one or more compounds expected to lack such toxicity. On the basis of the limited number of compounds studied all four tests, although varying in sensitivity, seem to correlate with the results of tests in other species and with known effects in man. Final validation of these acute tests, especially the CPK-MB, will require both further study of histopathologic effects and correlation with results from clinical trials of an extended list of agents.