title: Phase II study of a weekly 8-hour 5-fluorouracil and leucovorin infusion for patients with advanced colorectal cancer: dose adjusted according to its toxicity.
abstract: BACKGROUND
  5-fluorouracil (5-FU) clearly behaves as two different drugs according to the schedules for its administration. A weekly, 8-h 5-FU continuous infusion (CI) regimen may produce a dual effect, because it elicits both a high plasma 5-FU level and also a durable exposure to 5-FU, which may have the advantage of inhibiting both DNA synthesis and RNA activities. The plasma 5-FU level, however, cannot be monitored in most hospitals, so we initiated a pragmatic clinical trial with this weekly 8-h 5-FU Cl regimen and adjusted the drug's dose according to the detected toxicity.
  
  
  METHODS
  The initial dose of 5-FU was 1200 mg/m2 and this was escalated by 200 mg/m2 weekly, provided that no evidence of significant (grade 2 or greater) toxicity became apparent. Twenty-six patients entered the study from June 1998 to March 1999.
  
  
  RESULTS
  The median dose of 5-FU delivered was 1600 mg/m2. The major symptoms precluding dose escalation were nausea and vomiting. Seven patients demonstrated a partial response (26.9%), 11 patients revealed stable disease (42.3%) and eight exhibited progressive disease (30.8%).
  
  
  CONCLUSIONS
  This weekly 8-h CI 5-FU protocol with the adjustment of dose according to toxicity was not able to achieve the same 5-FU dose and response rate as in previous studies with pharmacokinetic monitoring of 5-FU levels. However, with the concurrent administration of intensive anti-emetic premedication, it is still possible to achieve adequate plasma 5-FU levels by adjusting the 5-FU dose according to elicited toxicity.
authors.affiliation: Department of Internal Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan. tsyangss@ms27.hinet.net
authors.forename: T S
authors.initials: TS
authors.lastname: Yang
authors.forename: K C
authors.initials: KC
authors.lastname: Hsu
authors.forename: H M
authors.initials: HM
authors.lastname: Wang
authors.forename: Y C
authors.initials: YC
authors.lastname: Lin
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003110:Colonic Neoplasms / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D012004:Rectal Neoplasms / Q000188:drug therapy*; D014840:Vomiting, Anticipatory / Q000209:etiology
chemical_list: D002955:Leucovorin; D005472:Fluorouracil