title: Hyperfractionated accelerated radiation therapy (HART) of 70.6 Gy with concurrent 5-FU/Mitomycin C is superior to HART of 77.6 Gy alone in locally advanced head and neck cancer: long-term results of the ARO 95-06 randomized phase III trial.
abstract: OBJECTIVE
  To report the long-term results of the ARO 95-06 randomized trial comparing hyperfractionated accelerated chemoradiation with mitomycin C/5-fluorouracil (C-HART) with hyperfractionated accelerated radiation therapy (HART) alone in locally advanced head and neck cancer.
  
  
  METHODS
  The primary endpoint was locoregional control (LRC). Three hundred eighty-four patients with stage III (6%) and IV (94%) oropharyngeal (59.4%), hypopharyngeal (32.3%), and oral cavity (8.3%) cancer were randomly assigned to 30 Gy/2 Gy daily followed by twice-daily 1.4 Gy to a total of 70.6 Gy concurrently with mitomycin C/5-FU (C-HART) or 16 Gy/2 Gy daily followed by twice-daily 1.4 Gy to a total dose of 77.6 Gy alone (HART). Statistical analyses were done with the log-rank test and univariate and multivariate Cox regression analyses.
  
  
  RESULTS
  The median follow-up time was 8.7 years (95% confidence interval [CI]: 7.8-9.7 years). At 10 years, the LRC rates were 38.0% (C-HART) versus 26.0% (HART, P=.002). The cancer-specific survival and overall survival rates were 39% and 10% (C-HART) versus 30.0% and 9% (HART, P=.042 and P=.049), respectively. According to multivariate Cox regression analysis, the combined treatment was associated with improved LRC (hazard ratio [HR]: 0.6 [95% CI: 0.5-0.8; P=.002]). The association between combined treatment arm and increased LRC appeared to be limited to oropharyngeal cancer (P=.003) as compared with hypopharyngeal or oral cavity cancer (P=.264).
  
  
  CONCLUSIONS
  C-HART remains superior to HART in terms of LRC. However, this effect may be limited to oropharyngeal cancer patients.
authors: Department of Radiation Oncology, Charité Universitätsmedizin Berlin, Germany. Electronic address: volker.budach@charite.de.
authors: Volker
authors: V
authors: Budach
authors: Department of Radiation Oncology, Charité Universitätsmedizin Berlin, Germany.
authors: Carmen
authors: C
authors: Stromberger
authors: Department of Radiation Oncology, University Hospital of Essen, Germany.
authors: Christoph
authors: C
authors: Poettgen
authors: Department of Radiation Oncology, University Hospital of Dresden, Germany.
authors: Michael
authors: M
authors: Baumann
authors: Department of Radiation Oncology, Heinrich Heine Universität Düsseldorf, Germany.
authors: Wilfried
authors: W
authors: Budach
authors: Department of Radiation Oncology, University Hospitals of Erlangen, Germany.
authors: Gerhard
authors: G
authors: Grabenbauer
authors: Department of Radiation Oncology, Charité Universitätsmedizin Berlin, Germany.
authors: Simone
authors: S
authors: Marnitz
authors: Department of Head and Neck Surgery, Charité Universitätsmedizin Berlin, Germany.
authors: Heidi
authors: H
authors: Olze
authors: Sostana GmbH, Berlin, Germany.
authors: Klaus-Dieter
authors: KD
authors: Wernecke
authors: Department of Radiation Oncology, Charité Universitätsmedizin Berlin, Germany.
authors: Pirus
authors: P
authors: Ghadjar
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D059248:Chemoradiotherapy / Q000379:methods*; D016001:Confidence Intervals; D019583:Dose Fractionation, Radiation; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006258:Head and Neck Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D006801:Humans; D007012:Hypopharyngeal Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage; D009062:Mouth Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy; D009959:Oropharyngeal Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy; D011159:Population Surveillance; D012044:Regression Analysis; D015996:Survival Rate
chemical_list: D016685:Mitomycin; D005472:Fluorouracil