Clinical significance of monitoring serum levels of 5-fluorouracil by continuous infusion in patients with advanced colonic cancer.
Serum concentrations of 5-fluorouracil (5-FU) given by continuous infusion to 19 patients with advanced colonic cancer were measured by an HPLC method, and steady-state concentration (SSc), area under the curve (AUC72) and total body clearance (Cl) were calculated as pharmacokinetic parameters. The serum level of 5-FU rapidly increased, reaching a plateau within 2 h after the start of administration. There were positive correlations between the dose and both SSc (r = 0.578, P less than 0.01) and AUC72 (r = 0.558, P less than 0.05). When the patients were divided into toxic and non-toxic groups according to the degree of toxicity, the values for SSc and AUC72 in the toxic group were significantly higher than those in non-toxic patients. The Cl value in the toxic group was also significantly different from that in the non-toxic group when data were calculated on a log scale. Furthermore, no differences in these parameters between effective and non-effective in these parameters between effective and non-effective groups were detected when the patients were divided into two groups according to anti-neoplastic responses. These results indicate that increased serum concentration does not always provide therapeutic benefits to patients receiving continuous infusions of 5-FU.
Department of Internal Medicine, National Cancer Center Hospital, Tokyo, Japan.
T
T
Yoshida
E
E
Araki
M
M
Iigo
T
T
Fujii
M
M
Yoshino
Y
Y
Shimada
D
D
Saito
H
H
Tajiri
H
H
Yamaguchi
S
S
Yoshida
D000328:Adult; D000368:Aged; D002851:Chromatography, High Pressure Liquid; D003110:Colonic Neoplasms / Q000097:blood / Q000188:drug therapy*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D006801:Humans; D007262:Infusions, Intravenous / Q000379:methods; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D012074:Remission Induction
D005472:Fluorouracil