Blomgren H, Edler D, Hallström M, Ragnhammar P
Karolinska Hospital, Stockholm, Sweden.
Anticancer Res. 1996 Sep-Oct;16(5A):2713-7.
Folinic acid (leucovorin) is frequently used to augment and modulate the clinical activity of 5-fluorouracil (5-FU) in patients with advanced gastrointestinal (Gl) cancer. However, there are conflicting opinions concerning the optimal doses for these patients, and whether folinic acid modulates the clinical activity of 5-FU in patients with non-Gl cancer. To elucidate these questions, model experiments have been performed on human tumor cell lines in vitro to determine the modulatory activity of various concentrations of folinic acid on 5-FU mediated cytotoxicity using a clonogenic assay. Three cell lines of colon cancer and 3 of glioblastoma origin were exposed to 5-FU alone or with folinic acid for 24 hours. It was observed that relatively low concentrations of folinic acid enhanced the cytotoxicity of 5-FU against the colon cancer lines whereas higher concentrations were less effective. Folinic acid did not enhance the 5-FU mediated killing of the glioma cell lines at any concentration (0.01-100 micrograms/ml). On the contrary, folinic acid seemed to counteract the cytotoxic effect of 5-FU in a reasonably dose-dependent fashion. These results may suggest that the value of folinic acid in the treatment of non-Gl cancer with 5-FU should be evaluated within the framework of controlled clinical trials, and that high doses of folinic acid may not necessarily be more effective than low.
亚叶酸（甲酰四氢叶酸）常用于增强和调节5-氟尿嘧啶（5-FU）对晚期胃肠道（GI）癌患者的临床活性。然而，对于这些患者的最佳剂量以及亚叶酸是否能调节5-FU对非GI癌患者的临床活性，存在相互矛盾的观点。为了阐明这些问题，已在体外对人肿瘤细胞系进行了模型实验，使用克隆形成试验来确定不同浓度的亚叶酸对5-FU介导的细胞毒性的调节活性。将三种结肠癌细胞系和三种胶质母细胞瘤源细胞系单独暴露于5-FU或与亚叶酸一起暴露24小时。观察到相对低浓度的亚叶酸增强了5-FU对结肠癌细胞系的细胞毒性，而较高浓度则效果较差。在任何浓度（0.01 - 100微克/毫升）下，亚叶酸均未增强5-FU对胶质瘤细胞系的杀伤作用。相反，亚叶酸似乎以合理的剂量依赖性方式抵消了5-FU的细胞毒性作用。这些结果可能表明，应在对照临床试验的框架内评估亚叶酸在与5-FU联合治疗非GI癌中的价值，并且高剂量的亚叶酸不一定比低剂量更有效。
