title: Placebo-controlled randomized trial of infusional fluorouracil during standard radiotherapy in locally advanced head and neck cancer.
abstract: OBJECTIVE
  To determine whether the addition of infusional fluorouracil (I-FU) to standard radiotherapy improves survival at acceptable toxicity in patients with locally advanced squamous cell head and neck cancer (SCHNC).
  
  
  METHODS
  Consenting patients with an Eastern Cooperative Oncology Group (ECOG) performance status < or = 2; with stage III or IV SCHNC of the oral cavity, oropharynx, hypopharynx, or larynx; and who were recommended for radiotherapy with curative intent received 66 Gy of radiation therapy delivered in 2-Gy fractions once daily 5 days per week for 6 1/2 weeks. Those in the experimental arm received I-FU 1.2 g/m2/d, as a 72-hour infusion in the first and third weeks of radiation. Saline infusions were used in the placebo arm.
  
  
  RESULTS
  One hundred seventy-five patients were randomized (88 to I-FU and 87 to placebo), and the treatment arms were well balanced. The complete response rate was 68% for I-FU and 56% for placebo (P = .04). The overall median survival duration was 33 months for I-FU and 25 months for placebo (P = .08). Progression-free survival also favored I-FU (P = .06). Toxicity was greater in I-FU patients, but did not interfere with the scheduled delivery or completion of radiation.
  
  
  CONCLUSIONS
  The addition of I-FU to standard radiation in SCHNC improved the complete response rate and was associated with beneficial trends in progression-free and overall survival compared with radiation alone. I-FU patients also experienced greater morbidity, but this did not compromise delivery of radiotherapy.
authors.affiliation: Hamilton Regional Cancer Centre, McMaster University, Ontario, Canada.
authors.forename: G P
authors.initials: GP
authors.lastname: Browman
authors.forename: C
authors.initials: C
authors.lastname: Cripps
authors.forename: D I
authors.initials: DI
authors.lastname: Hodson
authors.forename: L
authors.initials: L
authors.lastname: Eapen
authors.forename: J
authors.initials: J
authors.lastname: Sathya
authors.forename: M N
authors.initials: MN
authors.lastname: Levine
mesh_terms: D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy / Q000556:secondary; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D011879:Radiotherapy Dosage; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D005472:Fluorouracil