Low dose 1-hexylcarbamoyl-5-fluorouracil (HCFU) recommended for cirrhotic patients with hepatocellular carcinoma.
The metabolism of 1-hexylcarbamoyl-5-fluorouracil (HCFU), a drug prescribed for treating patients with hepatocellular carcinoma (HCC), was studied in relation to liver function, with the objective of clarifying the occurrence of any adverse side-effects on the central nervous system. Twenty-five HCC patients were administered 3.4 mg/kg HCFU once orally, after which the blood levels of HCFU and its derivatives (5-FU, CPEFU, CPRFU, HHCFU, OHCFU and F-beta-alanine) were serially measured using high performance liquid chromatography. The area under the concentration curve (AUC) of HCFU in the group of ICG R15 greater than or equal to 30% (group 2) was 5.35 +/- 1.73 h.micrograms/ml, a value which was significantly higher than the 2.60 +/- 1.19 h.micrograms/ml recorded for the group of ICG R15 less than 30% (group 1) (P less than 0.001). The AUC of HCFU had a significant positive correlation with the value of ICG R15 (P = 0.002) or the serum total bilirubin (P = 0.0005). The AUC of 5-FU showed no difference between the two groups. The AUC of CPRFU in group 2 was 0.16 +/- 0.25 h.micrograms/ml, a value significantly lower than the 0.48 +/- 0.39 h.micrograms/ml in group 1 (P = 0.023). There was no correlation between the AUC of other derivatives and the markers of liver function. These data suggest that, in patients with advanced cirrhosis, the accumulation of HCFU is related to the occurrence of side-effects from the administered drug, ingested over a long-term period. Therefore, when HCFU is given to cirrhotic patients with both HCC and 30% or more ICG R15, a careful monitoring for side-effects is required.
Takenaka
K
K
Second Department of Surgery, Kyushu University, Fukuoka, Japan.
Kanematsu
T
T
Shimada
M
M
Sugimachi
K
K
D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000378:metabolism / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000150:complications / Q000188:drug therapy*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000627:therapeutic use; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications*; D008113:Liver Neoplasms / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged
D000970:Antineoplastic Agents; C017367:carmofur; D005472:Fluorouracil