Relationship between in vitro tumor stem cell assay and in vivo antitumor activity using the P388 leukemia.
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.
Marsh
J C
JC
Developmental Therapeutics Program, National Cancer Institute, Bethesda, Maryland.
Shoemaker
R H
RH
Salmon
S E
SE
Kern
D H
DH
Venditti
J M
JM
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D003114:Colony-Forming Units Assay; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D006801:Humans; D007274:Injections, Intraperitoneal; D007941:Leukemia P388 / Q000188:drug therapy* / Q000473:pathology; D007942:Leukemia, Experimental / Q000188:drug therapy*; D051379:Mice; D014410:Tumor Stem Cell Assay
D000970:Antineoplastic Agents