Schroy P C, Cohen A, Winawer S J, Friedman E A
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
J Surg Oncol. 1990 Dec;45(4):217-23. doi: 10.1002/jso.2930450402.
Hepatic arterial infusion of fluorodeoxyuridine (FUdR) has demonstrated efficacy in the treatment of metastatic colorectal carcinoma of the liver. In this study, the direct cytotoxic effect of FUdR was measured on ten metastatic and two primary-site colorectal carcinomas in a primary culture assay system. Overall, clinically achievable concentrations of FUdR (0.4 to 4 microM) induced partial cell kill in 75% of tumors, including a greater than 50% reduction in viable tumor cell number in only two tumors and less than 50% in the remaining seven. Total cell kill was not observed in any tumor. Three tumors were resistant to these FUdR concentrations. Tumor sensitivity correlated with the size of the tumor growth fraction. Increasing the exposure time to FUdR from 3 to 7 days approximately doubled the magnitude of the response. 5-Flurouracil and cisplatin, at clinically achievable concentrations, were more toxic to metastatic tumor cells than FUdR. Because of the limited chemosensitivity of metastatic colorectal tumor cells to FUdR in vitro, we postulate that other mechanisms besides direct cytotoxicity contribute to the clinical efficacy of FUdR in vivo.
肝动脉灌注氟尿苷（FUdR）已证明对肝转移性结直肠癌的治疗有效。在本研究中，在原代培养分析系统中测定了FUdR对10例转移性和2例原发部位结直肠癌的直接细胞毒性作用。总体而言，临床上可达到的FUdR浓度（0.4至4 microM）在75%的肿瘤中诱导了部分细胞杀伤，其中仅2例肿瘤中存活肿瘤细胞数量减少超过50%，其余7例中减少不到50%。在任何肿瘤中均未观察到完全细胞杀伤。3例肿瘤对这些FUdR浓度耐药。肿瘤敏感性与肿瘤生长分数大小相关。将FUdR的暴露时间从3天增加到7天，反应幅度约增加一倍。在临床上可达到的浓度下，5-氟尿嘧啶和顺铂对转移性肿瘤细胞的毒性比FUdR更大。由于转移性结直肠肿瘤细胞在体外对FUdR的化学敏感性有限，我们推测除直接细胞毒性外的其他机制有助于FUdR在体内的临床疗效。
