title: Effect of combined treatment with micelle-incorporated cisplatin (NC-6004) and S-1 on human gastric cancer xenografts.
abstract: Combination therapy with S-1 and cisplatin (CDDP) is the standard chemotherapy for advanced gastric cancer in Japan; however, its administration requires hospitalization for hydration to prevent nephrotoxicity from CDDP. By contrast, NC-6004 appears to reduce the renal toxicity of CDDP and may be used on an outpatient basis. Thus, the effects of combined treatment with S-1 and NC-6004 were compared with those of S-1 and CDDP in a human gastric cancer model.In vitrocytotoxic effects were investigated in 44As3Luc, MKN45 and MKN74 human gastric cancer cell lines. The effects of NC-6004 and 5-fluorouracil (5-FU) were compared with the effects of CDDP and 5-FU using the combination index method. Thein vivoantitumor effects of S-1/NC-6004 and S-1/CDDP were evaluated in mice bearing 44As3Luc xenografts. Both combinations exhibited synergistic activity in MKN45 and MKN74 cells and additive effects in 44As3Luc cells. Moreover, thein vivoantitumor effects did not differ between the S-1/NC-6004 and S-1/CDDP treatment groups. However, a significantly lower body weight loss was observed in S-1/NC-6004-treated mice compared with the S-1/CDDP-treated mice. Our data warrant a clinical evaluation of S-1/NC-6004 combination therapy.
authors.affiliation: Division of Developmental Therapeutics, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Chiba 277-8577, Japan; Course of Advanced Clinical Research of Cancer, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan.
authors.forename: Masahisa
authors.initials: M
authors.lastname: Kudo
authors.affiliation: Division of Developmental Therapeutics, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Chiba 277-8577, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Division of Developmental Therapeutics, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Chiba 277-8577, Japan.
authors.forename: Yoshikatsu
authors.initials: Y
authors.lastname: Koga
authors.affiliation: Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hamaguchi
authors.affiliation: Course of Advanced Clinical Research of Cancer, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Akimoto
authors.affiliation: Division of Developmental Therapeutics, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Chiba 277-8577, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yasunaga
authors.affiliation: Division of Developmental Therapeutics, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Chiba 277-8577, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Matsumura
keywords: NC-6004; S-1; drug delivery system; enhanced permeability and retention effect; gastric cancer