High survival and organ function rates after primary chemoradiotherapy for intermediate-stage squamous cell carcinoma of the head and neck treated in a multicenter phase II trial

J Clin Oncol. 2006 Jul 20;24(21):3438-44. doi: 10.1200/JCO.2006.05.8529.


Purpose: Patients with intermediate-stage squamous cell carcinoma of the head and neck traditionally have been treated with initial surgical resection followed by radiotherapy (RT) alone or chemoradiotherapy. A previous study in this patient population reported a 91% locoregional control rate and 65% overall survival (OS) rate at 5 years, with chemoradiotherapy used as primary treatment. This study was undertaken to assess whether shortening treatment duration with hyperfractionated RT would be feasible and improve locoregional control, organ preservation, and progression-free survival.

Methods: Eligible patients with stage II or III disease received fluorouracil, hydroxyurea, and RT given twice daily on a week-on/week-off schedule. Quality-of-life scores were measured using three validated indexes.

Results: All 53 patients enrolled are included in the analysis, with a median follow-up of 42 months (range, 5 to 98 months). Grade 3 or 4 in-field mucositis was observed in 77% and 9%, respectively. No patients required surgical salvage at the primary tumor site (pathological complete response rate, 100%). The 3-year progression-free and OS rates are 67% and 78%, respectively. The 3-year disease-specific mortality rate is 7%. At the time of analysis, 87% of surviving patients do not require enteral feeding support. Quality-of-life and performance assessment indicated that, although acute treatment toxicities were severe, most patients returned to pretreatment function by 12 months.

Conclusion: Concurrent chemoradiotherapy with hyperfractionated RT is feasible in this patient population and yields high local control and cure rates. Compared with our historical control using once-daily fractionation, hyperfractionation is accompanied by increased acute in-field toxicity.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Analysis of Variance
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / physiopathology
  • Carcinoma, Squamous Cell / radiotherapy*
  • Chemotherapy, Adjuvant
  • Disease-Free Survival
  • Dose Fractionation, Radiation
  • Female
  • Fluorouracil / administration & dosage
  • Head and Neck Neoplasms / drug therapy*
  • Head and Neck Neoplasms / pathology
  • Head and Neck Neoplasms / physiopathology
  • Head and Neck Neoplasms / radiotherapy*
  • Humans
  • Hydroxyurea / administration & dosage
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Neoplasms, Second Primary / diagnosis
  • Quality of Life*
  • Radiotherapy Dosage
  • Radiotherapy, Adjuvant
  • Surveys and Questionnaires
  • Survival Analysis
  • Treatment Outcome


  • Fluorouracil
  • Hydroxyurea