Rustum Y M, Trave F, Zakrzewski S F, Petrelli N, Herrera L, Mittelman A, Arbuck S G, Creaven P J
Grace Cancer Drug Center, Roswell Park Memorial Institute, Buffalo, NY 14263.
NCI Monogr. 1987(5):165-70.
In vitro and in vivo studies have been carried out in mouse and human tumors to investigate the biochemical and pharmacologic basis for the selectivity of 5-fluorouracil (FUra) action. Combination chemotherapy with FUra and thymidine was performed to determine the therapeutic relevance of 5-fluorouridine triphosphate (FUTP) incorporation into RNA. The results of these studies indicate that modulation of FUra cytotoxicity by deoxythymidine (dThd) did occur but failed to produce any significant therapeutic advantages in patients with advanced colorectal cancer. Modulation of FUra bioactivation via the deoxyribonucleotide pathway by coadministration of high-dose folinic acid resulted in enhanced therapeutic response rate of gastrointestinal tumor patients. This manuscript summarizes the preclinical and clinical findings on the metabolic modulation of FUra activity by dThd and folinic acid.
已在小鼠和人类肿瘤中开展了体外和体内研究，以探究5-氟尿嘧啶（FUra）作用选择性的生化和药理学基础。进行了FUra与胸苷的联合化疗，以确定5-氟尿苷三磷酸（FUTP）掺入RNA的治疗相关性。这些研究结果表明，脱氧胸苷（dThd）对FUra细胞毒性的调节确实发生了，但在晚期结直肠癌患者中未能产生任何显著的治疗优势。通过联合给予高剂量亚叶酸经脱氧核苷酸途径调节FUra生物活化，可提高胃肠道肿瘤患者的治疗反应率。本手稿总结了关于dThd和亚叶酸对FUra活性进行代谢调节的临床前和临床研究结果。
