title: Phase I study of 5-fluorouracil administered by protracted venous infusion, leucovorin, and pelvic radiation therapy.
abstract: BACKGROUND
  This study was designed to assess the toxicity of pelvic radiation therapy, 5-fluorouracil (5-FU) administered by protracted venous infusion, and leucovorin.
  
  
  METHODS
  Pelvic radiation therapy consisted of 50.4-54 gray (Gy) administered in 28-30 fractions. Systemic treatment consisted of leucovorin (10 mg daily) administered orally and protracted venous infusion of 5-FU. The initial daily 5-FU dose was 150 mg/m(2). Dose escalations were planned in increments of 25 mg/m(2).
  
  
  RESULTS
  Forty eligible patients were registered, of whom 37 were evaluable for chemoradiotherapy-related toxicity. Grade 3 or 4 toxicity secondary to radiation therapy, protracted venous infusion of 5-FU, and leucovorin occurred in 2 of 17 patients at a daily 5-FU dose of 150 mg/m(2), in 5 of 10 patients at a daily 5-FU dose of 175 mg/m(2), and in 5 of 10 patients at a daily 5-FU dose of 200 mg/m(2). Diarrhea was dose-limiting in 7 of 8 patients with Grade 4 toxicity. Venous thrombosis, a treatment-related complication not directly related to chemotherapy or radiation therapy, occurred in 5 of the 40 patients entered into this study. Four thromboses occurred at the site of a central catheter. No thrombotic complications occurred in the last 7 patients, who were given warfarin orally (1 mg daily) during treatment.
  
  
  CONCLUSIONS
  Toxicity due to radiation therapy, protracted venous infusion of 5-FU, and leucovorin when 5-FU is given daily at a dose of 150 mg/m(2) is similar to that observed in current chemoradiotherapy regimens for patients with rectal carcinoma. This regimen will be considered as a possible investigational treatment arm of a future trial of adjuvant therapy for rectal carcinoma patients.
authors.affiliation: Mayo Clinic and Mayo Foundation, Rochester, Minnesota, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Martenson
authors.forename: T G
authors.initials: TG
authors.lastname: Shanahan
authors.forename: M J
authors.initials: MJ
authors.lastname: O'Connell
authors.forename: C D
authors.initials: CD
authors.lastname: Cobau
authors.forename: G
authors.initials: G
authors.lastname: Schroeder
authors.forename: P A
authors.initials: PA
authors.lastname: Burch
authors.forename: R
authors.initials: R
authors.lastname: Levitt
authors.forename: K M
authors.initials: KM
authors.lastname: Rowland
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy* / Q000532:radiotherapy*; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D002955:Leucovorin / Q000008:administration & dosage; D010388:Pelvis / Q000528:radiation effects; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D020246:Venous Thrombosis / Q000209:etiology
chemical_list: D002955:Leucovorin; D005472:Fluorouracil