International Journal of Cell Cloning, Vol 6, 60-68, Copyright © 1988 by AlphaMed Press
Relationship between in vitro tumor stem cell assay and in vivo antitumor activity using the P388 leukemia
JC Marsh, RH Shoemaker, SE Salmon, DH Kern and JM Venditti
Developmental Therapeutics Program, National Cancer Institute, Bethesda, Maryland.
The relationship between in vitro tumor stem cell sensitivity and in vivo
antitumor efficacy using 13 active antineoplastic agents was examined by
means of the intraperitoneal P388 mouse leukemia system. The doses, which
produced a 50% increase in life span after one, five and nine days of
treatment, were all significantly correlated with the in vitro
concentration producing a 70% reduction in colony formation during a
seven-day continuous drug exposure. The five-day correlation was the best,
followed by nine days and one day. Correlations were not improved by
corrections for either in vitro drug stability or toxicity (LD50). The
highly significant correlations observed in this simple retrospective
analysis provide a basis for the development of more sophisticated models
for the prediction of in vivo results from in vitro data.
