title: Relationship between 5-fluorouracil exposure and outcome in patients receiving continuous venous infusion with or without concomitant radiotherapy.
abstract: OBJECTIVE
  Toxicity and response are correlated with plasma 5-fluorouracil (5-FU) concentration in patients treated with 5-FU at a dose of 1000 mg m(-2) day(-1). Head and neck cancer patients are treated with various therapeutic regimens, including chemotherapy with 5-FU at a dose of 600 mg m(-2) day(-1) with radiotherapy. We investigated the plasma concentration-effect relationship for this regimen, with the aim of developing recommendations for dose adjustment.
  
  
  METHODS
  Patients received 5-FU at doses of 600 or 1000 mg m(-2) day(-1), as a continuous infusion over 4 or 5 days, with or without radiotherapy for the 600 mg m(-2) day(-1) regimen. The area under the curve (AUC) for 5-FU concentration was estimated, based on a single morning blood sample taken each day during treatment. AUC values were compared between patients with and without toxicity. This simplified method for AUC estimation was compared with the standard two-samples-per-day method in an independent group of 50 patients.
  
  
  RESULTS
  Forty-six patients, corresponding to 115 courses, were included in this prospective study. Considerable interindividual variability in estimated AUC was observed for both doses. Grade 3-4 toxicity occurred in 10 and 21% of patients given doses of 600 and 1000 mg m(-2) day(-1), respectively. Ths study confirmed the relationship between plasma 5-FU concentration and toxicity previously reported for 1000 mg m(-2) day(-1), but found no such relationship for the 600 mg m(-2) day(-1) regimen with concomitant radiotherapy.
  
  
  CONCLUSIONS
  Our results do not support the use of therapeutic drug monitoring to improve tolerance for the 600 mg m(-2) day(-1) regimen with concomitant radiotherapy. A simplified method is proposed for 5-FU monitoring for the 1000 mg m(-2) day(-1) regimen.
authors.affiliation: Department of Pharmacology, CHRU de Tours, Tours, France.
authors.forename: Maud
authors.initials: M
authors.lastname: Beneton
authors.forename: Sophie
authors.initials: S
authors.lastname: Chapet
authors.forename: Hélène
authors.initials: H
authors.lastname: Blasco
authors.forename: Bruno
authors.initials: B
authors.lastname: Giraudeau
authors.forename: Michèle
authors.initials: M
authors.lastname: Boisdron-Celle
authors.forename: Régine
authors.initials: R
authors.lastname: Deporte-Fety
authors.forename: Fabrice
authors.initials: F
authors.lastname: Denis
authors.forename: Bérangère
authors.initials: B
authors.lastname: Narcisso
authors.forename: Gilles
authors.initials: G
authors.lastname: Calais
authors.forename: Chantal
authors.initials: C
authors.lastname: Le Guellec
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000532:radiotherapy; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D008297:Male; D010865:Pilot Projects; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D005472:Fluorouracil