Efficiency of antitumor screening relative to activity criteria.

Well over 100,000 compounds have been screened by the National Cancer Institute (NCI) in mouse leukemia P388 in the search for new leads toward antineoplastic agents. The protocol for screening requires confirmation testing of compounds showing initial activity. By activity criteria being varied for initial and confirmation testing, it is possible to improve the efficiency of screening. The experimental variability of P388 screening was first determined by analysis of outcomes from 90 tests on each of 21 compounds of varied activity. By application of these results to NCI P388 data for 31,428 compounds adequately tested on a daily times five schedule, the consequences of using different activity thresholds were estimated. The results here may apply to those of other similar large-scale screening programs.