title: Evaluation of the individual 50% inhibitory area under the concentration curve of 5-fluorouracil based on the collagen gel droplet embedded culture drug sensitivity test in colorectal cancer.
abstract: We have previously reported the 5-fluorouracil (5-FU) sensitivity of cancer cells from colorectal cancer (CRC) patients using the collagen gel droplet embedded culture-drug sensitivity test (CD-DST) under multiple drug concentrations and contact durations. Moreover, the area under the concentration curve (AUC) and growth inhibition rate (IR) were combined, resulting in the AUC-IR curve, which was approximated to the logarithmic curve. In the present study, we used the AUC-IR curve to calculate the individualized AUCIR50, the AUC value that imparts 50% growth inhibition. Individual AUCIR50 was calculated in CRC patients, and its distribution was evaluated. The cumulative distribution of individual AUCIR50 was regressed over two lines (logarithmic scale). Among the 45 resectable CRC patients, those who achieved more than the individual AUCIR50 during post-operative 5-FU-based chemotherapy demonstrated a trend towards better disease-free survival compared to those who did not achieve AUCIR50. Of the Dukes' D patients (n=10), those who achieved more than twice the individual AUCIR50 during post-operative 5-FU-based chemotherapy demonstrated significantly better survival rates (p=0.05) than those who did not. In this study, the distribution of the individual AUCIR50 suggested that approximately 6% of patients demonstrated very low 5-FU sensitivity. Therefore, the individual AUCIR50 was useful in classifying good, intermediate and poor 5-FU response. Achievement of the individual AUCIR50 may be a prerequisite for individualized 5-FU-based adjuvant chemotherapy. As well, the early achievement of twice the individual AUCIR50 may indicate an improved prognosis in Dukes' D patients. The individual AUCIR50 using CD-DST is useful in determining the individualized chemotherapy of CRC patients, thus CD-DST has the potential to facilitate the establishment of individualized chemotherapy for CRC.
authors.affiliation: Department of Surgery, Tobu Chiiki Hospital, Tokyo Metropolitan Health and Medical Treatment Corporation, 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: Tomoo
authors.initials: T
authors.lastname: Watanabe
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kitajima
authors.forename: Masataka
authors.initials: M
authors.lastname: Tsuji
authors.forename: Akinori
authors.initials: A
authors.lastname: Nakatani
authors.forename: Noboru
authors.initials: N
authors.lastname: Nakayama
authors.forename: Takashi
authors.initials: T
authors.lastname: Marusasa
authors.forename: Satomi
authors.initials: S
authors.lastname: Mashiko
authors.forename: Isao
authors.initials: I
authors.lastname: Nagaoka
authors.forename: Shunji
authors.initials: S
authors.lastname: Futagawa