Abstract
5'-Deoxy-5-fluorouridine (5'-DFUR) is transformed to 5-fluorouracil (5-FU) by pyrimidine nucleoside phosphorylase (PyNPase) which shows high activity in the cancer. The drug then shows a high antitumor effect because of accumulation in the tumor. The biotransformation of 5'-DFUR was studied in 47 patients who were to undergo gastrectomy for gastric cancer, and the type of gastric cancer showing higher intracancerous accumulation was determined. 5'-DFUR was administered orally in a dose of 1200mg/day for 2 days before surgery, and another dose of 400mg was given orally 4 hr before surgery. The concentration of 5-FU and PyNPase activities in the cancers, non-cancerous gastric mucosas, metastatic regional lymph nodes, and negative regional lymph nodes, were determined. The concentration of 5-FU was significantly higher in the cancers than in the non-cancerous gastric mucosa. Clinicopathologic analysis revealed that the concentration of 5-FU tended to be higher in the invasive types, 8 cm or larger lesions, undifferentiated adenocarcinomas, and those with 7 infiltrative growth (INF) than in the others. The concentraton of 5-FU in the regional lymph nodes tended to be higher in the metastatic rather than negative lymphnodes. The concentration of 5-FU in the metastatic regional lymph nodes was determined according to histological type of lesion. It was higher in undifferentiated adenocarcinomas than in differentiated ones. PyNPase activity was also significantly elevated in the cancers and metastatic regional lymph nodes, and thus high. This indicates that 5'-DFUR has the property of being accumulated in the cancer, especialy the undifferentiated adenocarcinoma with a greater extent of invasion.
