Kudo Masahisa, Yamamoto Yoshiyuki, Koga Yoshikatsu, Hamaguchi Tetsuya, Akimoto Tetsuo, Yasunaga Masahiro, Matsumura Yasuhiro
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.
Division of Developmental Therapeutics, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Chiba 277-8577, Japan.
Mol Clin Oncol. 2016 Dec;5(6):817-822. doi: 10.3892/mco.2016.1070. Epub 2016 Nov 1.
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. cytotoxic 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. The antitumor 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, the antitumor 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.
在日本，S-1与顺铂（CDDP）联合疗法是晚期胃癌的标准化疗方案；然而，其给药需要住院进行水化以预防CDDP引起的肾毒性。相比之下，NC-6004似乎可降低CDDP的肾毒性，且可在门诊使用。因此，在人胃癌模型中比较了S-1与NC-6004联合治疗和S-1与CDDP联合治疗的效果。在44As3Luc、MKN45和MKN74人胃癌细胞系中研究了细胞毒性作用。使用联合指数法比较了NC-6004和5-氟尿嘧啶（5-FU）的效果与CDDP和5-FU的效果。在携带44As3Luc异种移植瘤的小鼠中评估了S-1/NC-6004和S-1/CDDP的抗肿瘤作用。两种联合治疗在MKN45和MKN74细胞中均表现出协同活性，在44As3Luc细胞中表现出相加作用。此外，S-1/NC-6004治疗组和S-1/CDDP治疗组的抗肿瘤效果没有差异。然而，与S-1/CDDP治疗的小鼠相比，S-1/NC-6004治疗的小鼠体重减轻明显更低。我们的数据支持对S-1/NC-6004联合疗法进行临床评估。
