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.
Keywords: National Cancer Chemotherapy Program, screening, dose-schedule,
first-order kinetics, cell-cycle specific, cell-cycle nonspecific, acute leukemia.