title: Concomitant chemoradiotherapy as primary therapy for locoregionally advanced head and neck cancer.
abstract: OBJECTIVE
  To achieve locoregional control of head and neck cancer, survival, and organ preservation using intensive concomitant chemoradiotherapy.
  
  
  METHODS
  This study was a phase II trial of chemoradiotherapy with cisplatin 100 mg/m(2) every 28 days, infusional fluorouracil 800 mg/m(2)/d for 5 days, hydroxyurea 1 g orally every 12 hours for 11 doses, and radiotherapy twice daily at 1.5 Gy/fraction on days 1 through 5 (total dose, 15 Gy). Five days of treatment were followed by 9 days of rest, during which time patients received granulocyte colony-stimulating factor. Five cycles (three with cisplatin) were administered over 10 weeks (total radiotherapy dose, </= 75 Gy). Adjuvant chemoprevention with retinoic acid and interferon alfa-2A was offered.
  
  
  RESULTS
  Seventy-six patients were treated (stage IV, 93%; N2, 54%; N3, 21%). At a median follow-up of 38 months, the 3-year progression-free survival is 72%, locoregional control 92%, systemic control 83%, and overall survival 55%. Toxicities included mucositis (grade 3, 45%; grade 4, 12%), neutropenia (grade 4, 39%), and thrombocytopenia (grade 4, 53%). Surgery at the primary site was performed in 13 patients, and 39 had neck dissection. A majority of patients declined adjuvant chemoprevention. Pharmacokinetic parameters were not prognostic of tumor control. Quality of life declined during treatment but returned from good to excellent by 12 months after treatment.
  
  
  CONCLUSIONS
  Intensive concomitant chemoradiotherapy leads to high locoregional control and survival rates with organ preservation and a reversal of the historical pattern of failure (distant > locoregional). Surgery after concomitant chemoradiotherapy is feasible. Compliance with adjuvant chemoprevention is poor. Identification of less toxic regimens and improved distant disease control emerge as important future research goals.
authors.affiliation: Departments of Medicine (Section of Hematology/Oncology), Radiation and Cellular Oncology, and Surgery, Committee of Clinical Pharmacology, and Comprehensive Cancer Center, University of Chicago, Chicago, IL 60637, USA. evokes@medicine.bsd.uchicago.edu
authors.forename: E E
authors.initials: EE
authors.lastname: Vokes
authors.forename: M S
authors.initials: MS
authors.lastname: Kies
authors.forename: D J
authors.initials: DJ
authors.lastname: Haraf
authors.forename: K
authors.initials: K
authors.lastname: Stenson
authors.forename: M
authors.initials: M
authors.lastname: List
authors.forename: R
authors.initials: R
authors.lastname: Humerickhouse
authors.forename: M E
authors.initials: ME
authors.lastname: Dolan
authors.forename: H
authors.initials: H
authors.lastname: Pelzer
authors.forename: L
authors.initials: L
authors.lastname: Sulzen
authors.forename: M E
authors.initials: ME
authors.lastname: Witt
authors.forename: Y C
authors.initials: YC
authors.lastname: Hsieh
authors.forename: B B
authors.initials: BB
authors.lastname: Mittal
authors.forename: R R
authors.initials: RR
authors.lastname: Weichselbaum
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D018450:Disease Progression; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy* / Q000601:surgery; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage; D008297:Male; D011788:Quality of Life; D011878:Radiotherapy / Q000009:adverse effects; D011879:Radiotherapy Dosage; D011994:Recombinant Proteins; D015996:Survival Rate; D014212:Tretinoin / Q000008:administration & dosage
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D014212:Tretinoin; D002945:Cisplatin; D005472:Fluorouracil; D006918:Hydroxyurea