title: Concomitant cisplatin significantly improves locoregional control in advanced head and neck cancers treated with hyperfractionated radiotherapy.
abstract: OBJECTIVE
  To determine whether the application of two courses of cisplatin simultaneously with hyperfractionated radiotherapy improves the outcome in locally advanced and/or node-positive nonmetastatic carcinomas of the head and neck, compared with hyperfractionated radiotherapy alone.
  
  
  METHODS
  From July 1994 to July 2000, 224 patients with squamous cell carcinomas of the head and neck (excluding nasopharynx and paranasal sinus) were randomly assigned to hyperfractionated radiotherapy (median dose, 74.4 Gy; 1.2 Gy twice daily) or the same radiotherapy combined with two cycles of concomitant cisplatin (20 mg/m2 on 5 days of weeks 1 and 5). The primary end point was time to any treatment failure; secondary end points were locoregional failure, metastatic relapse, overall survival, and late toxicity.
  
  
  RESULTS
  There was no difference in radiotherapy between both treatment arms (74.4 Gy in 44 days). The full cisplatin dose was applied in 93% and 71% of patients during the first and second treatment cycles, respectively. Acute toxicity was similar in both arms. Median time to any treatment failure was not significantly different between treatment arms (19 months for combined treatment and 16 months for radiotherapy only, respectively) and the failure-free rate at 2.5 years was 45% and 33%, respectively. Locoregional control and distant disease-free survival were significantly improved with cisplatin (log-rank test, P = .039 and .011, respectively). The difference in overall survival did not reach significance (log-rank test, P = .147). Late toxicity was comparable in both treatment groups.
  
  
  CONCLUSIONS
  The therapeutic index of hyperfractionated radiotherapy is improved by concomitant cisplatin.
authors.affiliation: Department of Radiation Oncology, University Hospital Zurich, Zurich, Switzerland. pia.huguenin@usz.ch
authors.forename: Pia
authors.initials: P
authors.lastname: Huguenin
authors.forename: Karl T
authors.initials: KT
authors.lastname: Beer
authors.forename: Abdelkarim
authors.initials: A
authors.lastname: Allal
authors.forename: Kaspar
authors.initials: K
authors.lastname: Rufibach
authors.forename: Corinne
authors.initials: C
authors.lastname: Friedli
authors.forename: Jacques Bernard
authors.initials: JB
authors.lastname: Davis
authors.forename: Bernhard
authors.initials: B
authors.lastname: Pestalozzi
authors.forename: Stephan
authors.initials: S
authors.lastname: Schmid
authors.forename: Armin
authors.initials: A
authors.lastname: Thöni
authors.forename: Mahmut
authors.initials: M
authors.lastname: Ozsahin
authors.forename: Jacques
authors.initials: J
authors.lastname: Bernier
authors.forename: Michael
authors.initials: M
authors.lastname: Töpfer
authors.forename: Roger
authors.initials: R
authors.lastname: Kann
authors.forename: Urs Richard
authors.initials: UR
authors.lastname: Meier
authors.forename: Peter
authors.initials: P
authors.lastname: Thum
authors.forename: Sabine
authors.initials: S
authors.lastname: Bieri
authors.forename: Markus
authors.initials: M
authors.lastname: Notter
authors.forename: Norbert
authors.initials: N
authors.lastname: Lombriser
authors.forename: Christoph
authors.initials: C
authors.lastname: Glanzmann
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D002945:Cisplatin / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005500:Follow-Up Studies; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009367:Neoplasm Staging; D011336:Probability; D011879:Radiotherapy Dosage; D018714:Radiotherapy, Adjuvant; D012016:Reference Values; D018570:Risk Assessment; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D013557:Switzerland; D016896:Treatment Outcome
chemical_list: D002945:Cisplatin