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.