title: Evaluation of 5-fluorouracil applicability by multi-point collagen gel droplet embedded drug sensitivity test.
abstract: The drug sensitivity of tumor cells is one of key issues to explore individualized therapy for cancer patients. One of such methods is in vitro anticancer drug sensitivity test which is generally based on one drug concentration and contact time. In this study, 5-fluorouracil (5-FU) sensitivity of cancer cells from colorectal cancer patients was evaluated by collagen gel droplet embedded drug sensitivity test (CD-DST) under multiple drug concentrations and contact durations. Cancer cells from 19 patients were measured for 9 drug concentration/contact time conditions (cohort 1) and from 34 patients were measured for 2 drug concentration/contact time conditions (cohort 2) using CD-DST. There was not significant difference in growth inhibition rate for 1.0 microg/ml for 24 h and 0.2 microg/ml for 120 h, which gives the same area under the curve (AUC) (p=0.832) in all 53 patients (cohort 1 and 2). In cohort 1, 9 conditions were successfully measured in 18 of 19 cohort 1 patients (94.7%). The drug concentrations and growth inhibition rate approximated to logarithmic curve for all 3 contact times and 50% inhibitory concentration (IC50) values at 3 contact times could be calculated in these 18 patients. Growth inhibition rate and AUC also approximated to logarithmic curve. These values varied several orders of magnitude among patients. In vitro antitumor effect of 5-FU depended on AUC in colorectal tumor and it might support the use of continuous infusion or oral therapy which generates significant AUC with manageable toxicity. Some patients demonstrating low 5-FU sensitivity could not be indicated for 5-FU based therapy, and non-5-FU therapy should be explored for them.
authors.affiliation: Department of Surgery, Tobu Chiiki Hospital, Tokyo Metropolitan Health and Medical Treatment Corporation, 5-14-1 Kameari, Katsushika-ku, Tokyo 125-8512, Japan. takumi-o@ma.kitanet.ne.jp
authors.forename: Takumi
authors.initials: T
authors.lastname: Ochiai
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nishimura
authors.forename: Hajime
authors.initials: H
authors.lastname: Noguchi
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kitajima
authors.forename: Yuko
authors.initials: Y
authors.lastname: Tsuruoka
authors.forename: Yuka
authors.initials: Y
authors.lastname: Takahashi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects*; D015331:Cohort Studies; D003094:Collagen; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor / Q000295:instrumentation / Q000379:methods*; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology*; D005782:Gels; D006801:Humans; D020128:Inhibitory Concentration 50; D008297:Male; D008875:Middle Aged; D015203:Reproducibility of Results; D013997:Time Factors; D014407:Tumor Cells, Cultured
chemical_list: D000964:Antimetabolites, Antineoplastic; D005782:Gels; D003094:Collagen; D005472:Fluorouracil