[5'-Deoxy-5-fluorouridine enzymatic activation from the masked compound to 5-fluorouracil in human malignant tissues]

It has been reported that 5'-DFUR is converted to 5-FU by uridine phosphorylase in experimental animal tumors. The conversion of thymidine, uridine and 5'-DFUR as substrates was studied in tumor and normal tissues of human and animals. A further series of studies was performed using 1-(2'-deoxy-beta-D-glucopyranosyl) thymine (GPT), a specific inhibitor of uridine phosphorylase. We found that this conversion in human tumors was catalyzed not by uridine phosphorylase but by thymidine phosphorylase. It was also confirmed that the enzyme activities in various human cancers were significantly several times higher than those in adjacent normal tissues. We succeeded in tried and isolating thymidine phosphorylase in a fairly pure form, from which enzyme Km values were calculated. After administration of 5'-DFUR intravenously or orally to patents, tissue and blood samples were collected by biopsy or surgical operation to determine the 5-FU level. The 5-FU levels were always higher in tumor tissues than in the blood or in normal tissues. Finally effective clinical efficacy was demonstrated by oral administration of 5'-DFUR.