title: Phase I and pharmacokinetic study of 5-fluorouracil administered by 5-day continuous infusion in patients with hepatocellular carcinoma.
abstract: OBJECTIVE
  In this study the maximum tolerated dose of 5-fluorouracil administered by 5-day (120-h) continuous infusion every 4 weeks was investigated and the pharmacokinetics in patients with hepatocellular carcinoma were evaluated.
  
  
  METHODS
  Patients with hepatocellular carcinoma no longer amenable to established forms of treatment were eligible for the study. The starting dose of 5-fluorouracil was 300 mg/m(2) per day and doses were escalated in 50 mg/m(2) per day increments in successive cohorts of three new patients if tolerated. Pharmacokinetic studies were performed at the time of the first course of therapy.
  
  
  RESULTS
  Enrolled in the study were 20 patients. The maximum tolerated dose was 500 mg/m(2) per day and the dose-limiting toxicity was stomatitis. Other toxicities were mild and well tolerated. Age, gender and associated liver cirrhosis were significant factors influencing 5-fluorouracil clearance. With regard to biochemical parameters, serum alanine aminotransferase and cholesterol levels were correlated with 5-fluorouracil clearance.
  
  
  CONCLUSIONS
  The maximum tolerated dose for 5-day continuous infusion of 5-fluorouracil in hepatocellular carcinoma patients was 500 mg/m(2) per day. The recommended dose for phase II studies using this schedule is 450 mg/m(2) per day. Furthermore, the pharmacokinetic data obtained in this study may be useful in determining chemotherapy dosage adjustments for reduction of toxicity.
authors.affiliation: Hepatobiliary and Pancreatic Oncology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. hiueno@ncc.go.jp
authors.forename: Hideki
authors.initials: H
authors.lastname: Ueno
authors.forename: Shuichi
authors.initials: S
authors.lastname: Okada
authors.forename: Takuji
authors.initials: T
authors.lastname: Okusaka
authors.forename: Masafumi
authors.initials: M
authors.lastname: Ikeda
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kuriyama
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000401:mortality; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D006801:Humans; D007262:Infusions, Intravenous; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged
chemical_list: D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil