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 pharmacokinetically equivalent to plasma levels and collagen gel droplet-embedded culture with a high cloning efficiency. We reported that the cell-killing effect of cell cycle phase-nonspecific drugs such as mitomycin C, cisplatin and Adriamycin depends on the area under the drug concentration-time curve (AUC). The plasma AUC values of these drugs were estimated 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 vitro sensitivity to a drug was compared with the in vivo response of the 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 between 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-negative rate and 83% of the correlation rate).
Inaba
M
M
Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo, Japan.
Tashiro
T
T
Sato
S
S
Ohnishi
Y
Y
Tanisaka
K
K
Kobayashi
H
H
Koezuka
M
M
D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002945:Cisplatin / Q000493:pharmacokinetics / Q000494:pharmacology; D003094:Collagen; D004317:Doxorubicin / Q000493:pharmacokinetics / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D016685:Mitomycin / Q000493:pharmacokinetics / Q000494:pharmacology; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D016685:Mitomycin; D004317:Doxorubicin; D003094:Collagen; D002945:Cisplatin