IN-VITRO IN-VIVO CORRELATION IN ANTICANCER DRUG-SENSITIVITY TEST USING AUC-BASED CONCENTRATIONS AND COLLAGEN GEL DROPLET-EMBEDDED CULTURE

To improve the ability of an in vitro drug sensitivity test to predict in vivo effects, we applied a drug concentration that was pharmacokin etically equivalent to plasma levels and collagen gel droplet-embedded culture with a high cloning efficiency. We reported that the cell-kil ling effect of cell cycle phase-nonspecific drugs such as mitomycin C, cisplatin and Adriamycin depends on the area under the drug concentra tion-time curve (AUC). The plasma AUC values of these drugs were estim ated after an injection into nude mice at the maximal tolerated doses (MTD). Tumor cells isolated from human tumor xenografts implanted into nude mice and cultured in collagen gel droplets were exposed to drugs under conditions that can reproduce the plasma AUC in vitro. The in v itro sensitivity to a drug was compared with the in vivo response of t he same tumor treated with the MTD of the drug. When the criterion of sensitivity was taken as 50% or less of the growth inhibition (growth rate of treated group/that of control group, T/C), the correlation bet ween the in vitro and in vivo growth inhibition of all 3 drugs tested was relatively high (86% of the true-positive rate, 82% of the true-ne gative rate and 83% of the correlation rate).