Borner M, Brunner K
Institut für Medizinische Onkologie, Inselspital Bern.
Schweiz Med Wochenschr. 1991 Aug 17;121(33):1149-56.
5-fluorouracil (5-FU) is the most effective drug in the treatment of advanced colorectal carcinoma and has definite activity in a variety of other solid tumors. However, remissions occur in only about 20% of the patients and usually are of short duration. Biochemical modulation is a way of enhancing the efficacy of 5-FU by manipulation of intracellular metabolic pathways. Leucovorin (LV) prolongs the inhibition of the key enzyme, thymidylate synthetase, by stabilizing the ternary complex with activated 5-FU, thus leading to "thymidine-less" death. Phase II trials showed promising response rates in colorectal, gastric, and breast cancer. This translated into prolonged survival and into an increased therapeutic index in some phase III studies comparing the combination 5-FU/LV with 5-FU monotherapy in colorectal cancer. The present article focuses on the pharmacological background of the therapy with 5-FU/LV, summarizes the clinical data and gives a short overview on other ways of increasing the therapeutic index of 5-FU.
5-氟尿嘧啶（5-FU）是治疗晚期结直肠癌最有效的药物，对多种其他实体瘤也有确切疗效。然而，只有约20%的患者会出现缓解，且缓解期通常较短。生化调节是通过操纵细胞内代谢途径来增强5-FU疗效的一种方法。亚叶酸（LV）通过与活化的5-FU稳定三元复合物来延长关键酶胸苷酸合成酶的抑制作用，从而导致“无胸腺嘧啶”死亡。II期试验显示在结直肠癌、胃癌和乳腺癌中有效率可观。在一些III期研究中，将5-FU/LV联合疗法与5-FU单药疗法用于结直肠癌治疗进行比较，结果表明联合疗法可延长生存期并提高治疗指数。本文重点介绍5-FU/LV治疗的药理学背景，总结临床数据，并简要概述提高5-FU治疗指数的其他方法。
