Evaluation of 5-fluorouracil applicability by the collagen gel droplet embedded drug sensitivity test with area under the curve analysis.
We have evaluated the 5-fluorouracil sensitivity of cancer cells from colorectal cancer patients using the collagen gel droplet embedded drug sensitivity test under multiple drug concentrations and contact durations. After converting drug concentration and contact time to the area under the curve (AUC) and plotting against the growth inhibition rate, the correlation between AUC and the growth inhibition rates was approximated to the logarithmic regression curve. In this study, to further validate the reliability of the regression curve, the growth inhibition rate was calculated from the regression curve and the actual growth inhibition rate was compared at AUC of 48 mug h/ml. No significant difference was observed in the growth inhibition rates between the two groups by paired t-test (P=0.590). A strong positive correlation was found between the two groups by regression analysis (y=0.7555x+10.514, R=0.8236). This result strongly suggests that in-vitro antitumor effect of 5-fluorouracil depends on the AUC in colorectal cancer and the AUC-inhibition rate curve is reliable. We can obtain the inhibition rate from AUC and vice versa using the AUC-inhibition rate curve. We can also calculate the individualized AUCIR50, AUC value that gives 50% growth inhibition, using the AUC-inhibition rate curve. This could be useful to establish individualized chemotherapy using the collagen gel droplet embedded drug sensitivity test.
Ochiai
Takumi
T
Department of Surgery, Tobu Chiiki Hospital, Tokyo Metropolitan Health and Medical Treatment Corporation, Juntendo University School of Medicine, Tokyo, Japan. takumi-o@ma.kitanet.ne.jp
Nishimura
Kazuhiko
K
Noguchi
Hajime
H
Watanabe
Tomoo
T
Kitajima
Masayuki
M
Konishi
Nanami
N
Sato
Go
G
Nagaoka
Isao
I
Futagawa
Shunji
S
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019540:Area Under Curve; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004341:Drug Evaluation / Q000379:methods; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D005260:Female; D005472:Fluorouracil / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D014407:Tumor Cells, Cultured
D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil