A pharmacological pilot study: application of an intermittent schedule of oral uracil and ftorafur (UFT) for hepatocellular carcinoma patients.
Patients with hepatocellular carcinoma (HCC) are highly compromised by failing liver function. To retain good compliance in the administration of uracil and ftorafur (UFT) in such patients, an intermittent schedule for oral administration of UFT was expected to have the same effect as daily continuous use without affecting liver function. A pharmacological pilot study was carried out to confirm the efficacy of this schedule. Sixteen patients with HCC who underwent hepatectomy were given UFT 200 mg b.i.d. for five consecutive days. Blood samples were drawn before the last administration of UFT and at the operation (2 days after the last administration of UFT), and the tumor and adjacent liver tissue were collected. The concentration of ftorafur (FT), 5-fluorouracil (FUra) and uracil (Ura) in serum and liver tissue were measured. Oral administration of UFT 200 mg b.i.d. resulted in a trough level of FT, FUra and Ura in serum of 9.4 micrograms/ml, 13.3 ng/ml and 64.2 ng/ml, respectively. At the operation, FT and FUra in serum had decreased significantly. However, FUra in tissue was still higher than that in serum, in contrast to the results for FT and Ura. There was no difference in the concentration of FUra between the tumors and adjacent liver tissues. No side effect was noted in any of the patients. These results indicated that an intermittent schedule for the administration of oral UFT is not only tolerable but also effective because a sufficient concentration of FUra in the liver tissue is reached and maintained.
Une
Y
Y
First Department of Surgery, Hokkaido University School of Medicine, Japan.
Kamiyama
T
T
Nishibe
M
M
Shimamura
T
T
Haneda
T
T
Nakanishi
K
K
Uchino
J
J
D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D005260:Female; D006498:Hepatectomy; D006801:Humans; D007677:Kidney Function Tests; D008111:Liver Function Tests; D008113:Liver Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010865:Pilot Projects; D005641:Tegafur / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014498:Uracil / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use*
D000964:Antimetabolites, Antineoplastic; D005641:Tegafur; D014498:Uracil