[A study of preoperative administration of 5'-DFUR in patients with colo-rectal cancer].

For the purpose to assess tumor-selectivity of doxifluridine (5'-DFUR), an anticancer drug of fluorinated pyrimidine class, the authors conducted a clinical-pharmacological study with the drug. The subjects in the present study, 26 patients with colorectal cancer received surgeries, were preoperatively administered 5'-DFUR orally at either doses of 800 or 1,200 mg/day for 3 days followed by oral administration of the drug at a dose of 400 mg 4-6 hrs before operation. The tissues were collected from specimens removed at operations and we measured both the activities of pyrimidine nucleoside phosphorylase (PyNPase), an activating enzyme for 5'-DFUR, and 5-FU concentrations in the tissue samples. The PyNPase activities showed higher levels in tumor tissues and regional lymph nodes than in normal tissues adjacent to the tumors. The 5-FU concentrations were: 102.7 ng/g in tumor tissues, 12.5 ng/g in normal tissues adjacent to the tumors, 97.6 ng/g in metastatic lymph nodes, and 7.3 ng/g in normal lymph nodes. In other words, the 5-FU concentrations were significantly (p < 0.01) higher in either of tumor tissues and metastatic lymph nodes than in the rests. The 5-FU concentrations in the sera were also extremely low. The results above clearly indicate that 5'-DFUR has a high selectivity for tumors.

[Study of tissue drug concentration of fluorinated pyrimidine anticancer drugs--comparison of 5'DFUR and UFT].

In order to verify the tumor-selective toxicity of fluorinated pyrimidine anticancer drugs, we conducted an investigation of the clinical pharmacology of two of these drugs, 5'DFUR and UFT. 5'DFUR was administered to 8 patients and UFT to 8 other patients in respective dosages of 800-1,000 mg/day and 400-600 mg/day an average of 6 days before the patients underwent surgery for cancer of the large bowel, and the concentrations of these drugs in tissue were then measured. No 5'DFUR whatsoever was detected in serum, the lymphnodes, normal large bowel tissue, or cancerous large bowel tissue after administration of this drug. Moreover, levels of the active substance, 5-FU, after administration of 5'-DFUR were low in serum, the lymphnodes, normal large bowel tissue (0.033 +/- 0.024 microgram/g), and cancerous large bowel tissue (0.034 +/- 0.020 microgram/g), and no difference was observed between normal and cancerous large intestine tissue. On the other hand, tegafur was detected in all of the tissues following the administration UFT, and the concentration of 5-FU was significantly high, particularly in cancerous large bowel tissue (0.108 +/- 0.057 microgram/g) compared to normal sites (0.044 +/- 0.048 microgram/g) (p less than 0.05). The above results indicate that UFT is a promising drug for use in chemotherapy for cancer of the large bowel.

[Study on the correlation between tissue uptake of anticancer agents and prognosis -- with special reference to Tegafur].

Advanced gastric cancer cases (42 cases) undergone gastrectomy were studied on the correlation between tissue uptakes and prognosis. The patients were administrated Tegafur preoperatively and tissue samples were obtained intraoperatively, 5-FU levels in tumor and lymph node were measured by GCMF. The patients, being measured 5-FU uptake by tissue and received Tegafur over 60 g as postoperative adjuvant chemotherapy, were divided into two groups; namely, one with 5-FU up take by tumor tissue and lymph node was higher than 0.05 mcg/g and the other with lower than 0.05 mcg/g. Both groups showed no significant difference in background factors. Each survival rate was calculated by Kaplan-Meier method and examined by generalized Wilcoxon method. As the result, there was no significant correlation in the 5-FU uptake by tumor and prognosis, but prolongation of survival rate in the group of 5-FU uptake by lymph node over 0.05 mcg/g was suggested.