title: Individualized chemotherapy for colorectal cancer based on the collagen gel droplet-embedded drug sensitivity test.
abstract: The leucovorin (FOL) and fluorouracil (5-FU) plus oxaliplatin (l-OHP; FOLFOX) or FOL and 5-FU plus irinotecan (SN-38; FOLFIRI) regimens with or without molecularly-targeted drugs are widely used as first-line chemotherapy in the treatment of advanced colorectal cancer (CRC). Whether FOLFOX or FOLFIRI is administered first is not significant, however, it is essential that full administration of the targeted dosages of all 3 drugs, 5-FU, l-OHP and SN-38, is achieved. However, this is not always possible and second-line chemotherapy must be abandoned in certain cases. Where possible, the most effective regimen should be selected as the first line of treatment. The aim of this study was to determine whether first-line chemotherapy may be individualized using the collagen gel droplet-embedded drug sensitivity test (CD-DST). Specimens of primary tumors were obtained from 43 CRC patients who had received no preoperative chemotherapy. Informed consent to measure drug sensitivity was obtained from all patients. The CD-DST allows evaluation of drug sensitivity using isolated, 3-dimensionally cultured tumor cells in a small collagen gel droplet. The CD-DST was performed and the growth inhibition rate (IR) was obtained under incubation conditions (5-FU with l-OHP at 6.0 and 3.0 μg/ml, or 5-FU with SN-38 at 6.0 and 0.2 μg/ml, respectively, for 24 h). The cumulative distributions of the growth IRs under each condition were evaluated based on the evidence that the clinical response rates to FOLFOX and FOLFIRI were almost the same. Individualization of first-line treatment was possible in all patients, with FOLFOX and FOLFIRI showing higher efficacy in 26 and 15 patients, respectively, and equal efficacy in 2 cases. This method has the potential to facilitate the establishment of individualized first-line chemotherapy for CRC and improve the prognosis in such patients.
authors.affiliation: Departments of Surgery and.
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: Akinori
authors.initials: A
authors.lastname: Nakatani
authors.forename: Takashi
authors.initials: T
authors.lastname: Inou
authors.forename: Marie
authors.initials: M
authors.lastname: Washio
authors.forename: Naoki
authors.initials: N
authors.lastname: Sakuyama
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Sato
authors.forename: Kenji
authors.initials: K
authors.lastname: Kishine
authors.forename: Takanori
authors.initials: T
authors.lastname: Ochi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Okubo
authors.forename: Shunji
authors.initials: S
authors.lastname: Futagawa
authors.forename: Satomi
authors.initials: S
authors.lastname: Mashiko
authors.forename: Isao
authors.initials: I
authors.lastname: Nagaoka