title: A phase II trial of weekly high dose continuous infusion 5-fluorouracil plus oral leucovorin in patients with advanced colorectal cancer. The Spanish Cooperative Group for Gastrointestinal Tumor Therapy (TTD).
abstract: BACKGROUND
  In a previous Phase II trial, the authors showed that a weekly continuous infusion of 5-fluorouracil (5-FU) at a dose of 3.5 g/m2 for 48 hours is an active treatment for advanced colorectal cancer. The overall response rate was 38.5%, and the median survival was 12 months. These data were comparable to those achieved by biochemical modulation of 5-FU with leucovorin. To study the modulation of this weekly, high dose, continuous infusion 5-FU with oral leucovorin, a new Phase II trial was planned.
  
  
  METHODS
  From December 1991 to July 1992, 43 previously untreated patients with measurable advanced colorectal cancer were included in a multicenter study. They received on an outpatient basis 5-FU at a weekly dose of 3 g/m2 by continuous infusion for 48 hours until progression or toxicity. Oral leucovorin (60 mg every 6 hours) also was given during the infusion of 5-FU.
  
  
  RESULTS
  Patients received a median dose intensity of 5-FU of 2.2 g/m2/week (range, 0.76-3 g/m2/week). One complete response and 11 partial responses were observed. The overall response rate was 29% (95% confidence interval [CI], 16-45%). Median time to progression was 7 months, and the median survival was 15 months. World Health Organization Grades 3 and 4 diarrhea were observed in 19 (45%) and 6 (14%) patients, respectively. Grade 3 mucositis also was observed in 10 (24%) patients, and Grade 4 mucositis was observed in 1. Grade 3 nausea and vomiting were reported in seven (17%) patients. Grade 3 hand-foot syndrome was detected in only two (2.5%) patients. No leukopenia or thrombocytopenia was observed.
  
  
  CONCLUSIONS
  Oral leucovorin modulation of a weekly 48-hour infusion of 5-FU at a dose of 3 g/m2 of leucovorin is a toxic regimen, always requiring dose reduction, with diarrhea and mucositis as the main limiting toxicities. Its antitumor activity does not seem superior to that observed with a weekly 48-hour infusion of 5-FU alone at a dose of 3.5 g/m2.
authors.affiliation: Hospital Clínico Provincial, Córdoba, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Aranda
authors.forename: A
authors.initials: A
authors.lastname: Cervantes
authors.forename: J
authors.initials: J
authors.lastname: Dorta
authors.forename: E
authors.initials: E
authors.lastname: Blanco
authors.forename: C
authors.initials: C
authors.lastname: Fernández-Martos
authors.forename: J J
authors.initials: JJ
authors.lastname: Cruz-Hernandez
authors.forename: A
authors.initials: A
authors.lastname: Carrato
authors.forename: R
authors.initials: R
authors.lastname: Gonzalez-Mancha
authors.forename: J
authors.initials: J
authors.lastname: García-Conde
authors.forename: E
authors.initials: E
authors.lastname: Díaz-Rubio
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage*; D006801:Humans; D007262:Infusions, Intravenous; D002955:Leucovorin / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis
chemical_list: D002955:Leucovorin; D005472:Fluorouracil