title: Randomized phase III study of 2 cisplatin-based chemoradiation regimens in locally advanced head and neck squamous cell carcinoma: impact of changing disease epidemiology on contemporary trial design.
abstract: BACKGROUND
  Chemoradiotherapy results in excellent outcomes in locally advanced head and neck squamous cell carcinoma (HNSCC). This trial compared 2 chemoradiotherapy regimens.
  
  
  METHODS
  Patients with locally advanced HNSCC were treated with radiation (70-74.4 Gy), and randomized to arm A: cisplatin 100 mg/m(2) on radiotherapy (RT) days 1, 22, and 43, or arm B: cisplatin (20 mg/m(2) /day) and 5-fluorouracil (5-FU; 1000 mg/m(2) /day) continuous 96-hour infusions on RT weeks 1 and 4. The primary endpoint was relapse-free survival (RFS).
  
  
  RESULTS
  Between February 2008 and October 2011, 69 patients were enrolled in this study. The study prematurely closed when a scheduled interim analysis showed superior outcomes in both arms and futility of continuation. Eighty-three percent of patients had oropharyngeal cancer, of these, 86% were human papillomavirus (HPV)/p16+. The 3-year Kaplan-Meier outcome estimates (median follow-up, 41 months) for arms A and B were: RFS 87% versus 80% (p = .24), overall survival 97% versus 85% (p = .013), locoregional control 96% versus 94% (p = .52), and distant metastatic control 91% versus 87% (p = .9).
  
  
  CONCLUSIONS
  Multiagent was not superior to single-agent chemoradiotherapy. Overrepresentation of HPV/p16+ patients resulted in better than expected outcomes.
authors.affiliation: University of Washington, Seattle Cancer Care Alliance, Seattle, Washington.
authors.forename: Cristina P
authors.initials: CP
authors.lastname: Rodriguez
authors.affiliation: Cleveland Clinic Foundation, Cleveland, Ohio.
authors.forename: David J
authors.initials: DJ
authors.lastname: Adelstein
authors.affiliation: Cleveland Clinic Foundation, Cleveland, Ohio.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Rybicki
authors.affiliation: Ohio State University, Columbus, Ohio.
authors.forename: Panayiotis
authors.initials: P
authors.lastname: Savvides
authors.affiliation: Cleveland Clinic Foundation, Cleveland, Ohio.
authors.forename: Jerrold P
authors.initials: JP
authors.lastname: Saxton
authors.affiliation: Cleveland Clinic Foundation, Cleveland, Ohio.
authors.forename: Shlomo A
authors.initials: SA
authors.lastname: Koyfman
authors.affiliation: Cleveland Clinic Foundation, Cleveland, Ohio.
authors.forename: John F
authors.initials: JF
authors.lastname: Greskovich
authors.affiliation: Case Western Reserve University, Seidman Cancer Institute, Cleveland, Ohio.
authors.forename: Min
authors.initials: M
authors.lastname: Yao
authors.affiliation: Cleveland Clinic Foundation, Cleveland, Ohio.
authors.forename: Joseph
authors.initials: J
authors.lastname: Scharpf
authors.affiliation: Case Western Reserve University, Seidman Cancer Institute, Cleveland, Ohio.
authors.forename: Pierre
authors.initials: P
authors.lastname: Lavertu
authors.affiliation: Cleveland Clinic Foundation, Cleveland, Ohio.
authors.forename: Benjamin G
authors.initials: BG
authors.lastname: Wood
authors.affiliation: Cleveland Clinic Foundation, Cleveland, Ohio.
authors.forename: Brian B
authors.initials: BB
authors.lastname: Burkey
authors.affiliation: Cleveland Clinic Foundation, Cleveland, Ohio.
authors.forename: Robert R
authors.initials: RR
authors.lastname: Lorenz
authors.affiliation: Case Western Reserve University, Seidman Cancer Institute, Cleveland, Ohio.
authors.forename: Rod P
authors.initials: RP
authors.lastname: Rezaee
authors.affiliation: Case Western Reserve University, Seidman Cancer Institute, Cleveland, Ohio.
authors.forename: Chad A
authors.initials: CA
authors.lastname: Zender
authors.affiliation: Cleveland Clinic Foundation, Cleveland, Ohio.
authors.forename: Denise I
authors.initials: DI
authors.lastname: Ives
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000401:mortality* / Q000473:pathology / Q000628:therapy*; D059248:Chemoradiotherapy / Q000379:methods*; D002945:Cisplatin / Q000008:administration & dosage*; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006258:Head and Neck Neoplasms / Q000401:mortality* / Q000473:pathology / Q000628:therapy*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000473:pathology / Q000628:therapy; D009367:Neoplasm Staging; D011879:Radiotherapy Dosage; D018570:Risk Assessment; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D002945:Cisplatin
keywords: chemoradiation; head and neck cancer; human papillomavirus (HPV); oropharynx; squamous cell carcinoma