A pharmacological study of the weekday-on/weekend-off oral UFT schedule in colorectal cancer patients.
OBJECTIVE
The new weekday-on/weekend-off schedule for oral UFT administration consists of its administration for 5 consecutive days followed by 2 days off the drug. The intratumor 5-FU (5-fluorouracil) concentration has been reported to be correlated to the tumor response in patients treated with intravenous 5-FU. The aim of this study was to investigate the pharmacokinetics during the 2 days off the drug in cancer patients treated with the weekday-on/weekend-off schedule for oral UFT.


METHODS
The subjects were 24 colorectal cancer patients. They were divided into three groups, and were all given UFT, 600 mg/day, for 5 days before surgery. Surgery was performed 2, 24, or 48 h after the final dose of UFT. The 5-FU concentrations in the serum, tumor, and in the normal mucosa were measured.


RESULTS
The serum 5-FU concentrations after the final dose of UFT were: 23 +/- 12 ng/ml (mean +/- SD) at 2 h, 7 +/- 3 ng/ml at 24 h, and 6 +/- 3 ng/ml at 48 h. The intratumor 5-FU concentrations were: 113 +/- 45 ng/g at 2 h, 54 +/- 20 ng/ml at 24 h, and 54 +/- 35 ng/ml at 48 h, and the concentrations in the normal mucosa were: 36 +/- 15 ng/g (mean +/- SD) at 2 h, 17 +/- 6 ng/ml at 24 h, and 18 +/- 6 ng/ml at 48 h after the final dose. While the serum 5-FU concentration decreased to very low levels by 24 h after the final dose of UFT, the intratumor 5-FU concentrations were maintained at more than 50 ng/g at least until 48 h after the final dose. The 5-FU concentrations in the normal mucosa were maintained at about one third of the intratumor concentrations at all time points.


CONCLUSIONS
Although the weekday-on/weekend-off schedule for UFT administration included intermittent 2-day drug-off periods, this pharmacokinetic study revealed that the 5-FU concentrations in the tumor were maintained at much higher levels than in the serum throughout these periods.
Sadahiro
S
S
Department of Surgery, Tokai University, School of Medicine, Bohseidai Isehara-shi, Kanagawa 259-1193, Japan. sadahiro@is.icc.u-tokai.ac.jp
Suzuki
T
T
Kameya
T
T
Iwase
H
H
Tajima
T
T
Makuuchi
H
H
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D015179:Colorectal Neoplasms / Q000097:blood / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D005472:Fluorouracil / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D005641:Tegafur / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D014498:Uracil / Q000008:administration & dosage* / Q000493:pharmacokinetics*
D000970:Antineoplastic Agents; D004338:Drug Combinations; C096910:UFT(R) drug; D005641:Tegafur; D014498:Uracil; D005472:Fluorouracil