title: Randomized trial of radiation therapy versus concomitant chemotherapy and radiation therapy for advanced-stage oropharynx carcinoma.
abstract: BACKGROUND
  We designed a randomized clinical trial to test whether the addition of three cycles of chemotherapy during standard radiation therapy would improve disease-free survival in patients with stages III and IV (i.e., advanced oropharynx carcinoma).
  
  
  METHODS
  A total of 226 patients have been entered in a phase III multicenter, randomized trial comparing radiotherapy alone (arm A) with radiotherapy with concomitant chemotherapy (arm B). Radiotherapy was identical in the two arms, delivering, with conventional fractionation, 70 Gy in 35 fractions. In arm B, patients received during the period of radiotherapy three cycles of a 4-day regimen containing carboplatin (70 mg/m(2) per day) and 5-fluorouracil (600 mg/m(2) per day) by continuous infusion. The two arms were equally balanced with regard to age, sex, stage, performance status, histology, and primary tumor site.
  
  
  RESULTS
  Radiotherapy compliance was similar in the two arms with respect to total dose, treatment duration, and treatment interruption. The rate of grades 3 and 4 mucositis was statistically significantly higher in arm B (71%; 95% confidence interval [CI] = 54%-85%) than in arm A (39%; 95% CI = 29%-56%). Skin toxicity was not different between the two arms. Hematologic toxicity was higher in arm B as measured by neutrophil count and hemoglobin level. Three-year overall actuarial survival and disease-free survival rates were, respectively, 51% (95% CI = 39%-68%) versus 31% (95% CI = 18%-49%) and 42% (95% CI = 30%-57%) versus 20% (95% CI = 10%-33%) for patients treated with combined modality versus radiation therapy alone (P =.02 and.04, respectively). The locoregional control rate was improved in arm B (66%; 95% CI = 51%-78%) versus arm A (42%; 95% CI = 31%-56%).
  
  
  CONCLUSIONS
  The statistically significant improvement in overall survival that was obtained supports the use of concomitant chemotherapy as an adjunct to radiotherapy in the management of carcinoma of the oropharynx.
authors.affiliation: G. Calais, Centre Hospitalier Universitaire Tours, France. calais@med.univ-tours.fr
authors.forename: G
authors.initials: G
authors.lastname: Calais
authors.forename: M
authors.initials: M
authors.lastname: Alfonsi
authors.forename: E
authors.initials: E
authors.lastname: Bardet
authors.forename: C
authors.initials: C
authors.lastname: Sire
authors.forename: T
authors.initials: T
authors.lastname: Germain
authors.forename: P
authors.initials: P
authors.lastname: Bergerot
authors.forename: B
authors.initials: B
authors.lastname: Rhein
authors.forename: J
authors.initials: J
authors.lastname: Tortochaux
authors.forename: P
authors.initials: P
authors.lastname: Oudinot
authors.forename: P
authors.initials: P
authors.lastname: Bertrand
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D017024:Chemotherapy, Adjuvant; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009959:Oropharyngeal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D011879:Radiotherapy Dosage; D018714:Radiotherapy, Adjuvant; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D016190:Carboplatin; D005472:Fluorouracil