Abstract

In 1953, the United States National Institutes, including the National Cancer Institute, were assembled in Bethesda. In 1955, a National Cancer Chemotherapy Program was established and scientific panels were formed with the participation of basic and clinical scientists and statisticians. An extensive experimental and clinical drug development program was initiated at the National Cancer Institute. Animal screening models predictive of anticancer drug activity were studied and criteria for preclinical toxicology and activity were developed. Important concepts emerged from experimental studies that influenced cancer therapy, including the dose-schedule and first-order kinetics principles, and the effects of anticancer agents on proliferating and resting cells. Under the leadership of Dr. Zubrod, the activities of a triumvirate of clinical scientists, Doctors Frei, Freireich and Holland, initially focussed on the treatment of acute leukemia, following up on Holland’s innovative use of a two-drug combination.