title: Concomitant chemoradiotherapy versus acceleration of radiotherapy with or without concomitant chemotherapy in locally advanced head and neck carcinoma (GORTEC 99-02): an open-label phase 3 randomised trial.
abstract: BACKGROUND
  Concomitant chemoradiotherapy and accelerated radiotherapy independently improve outcomes for patients with locally advanced head and neck squamous-cell carcinoma (HNSCC). We aimed to assess the efficacy and safety of a combination of these approaches.
  
  
  METHODS
  In our open-label phase 3 randomised trial, we enrolled patients with locally advanced, stage III and IV (non-metastatic) HNSCC and an Eastern Cooperative Oncology Group performance status of 0-2. We randomly allocated patients centrally with a computer program (with centre, T stage, N stage, and localisation as minimisation factors) in a 1:1:1 ratio to receive conventional chemoradiotherapy (70 Gy in 7 weeks plus three cycles of 4 days' concomitant carboplatin-fluorouracil), accelerated radiotherapy-chemotherapy (70 Gy in 6 weeks plus two cycles of 5 days' concomitant carboplatin-fluorouracil), or very accelerated radiotherapy alone (64·8 Gy [1·8 Gy twice daily] in 3·5 weeks). The primary endpoint, progression-free survival (PFS), was assessed in all enrolled patients. This trial is completed. The trial is registered with ClinicalTrials.gov, number NCT00828386.
  
  
  RESULTS
  Between Feb 29, 2000, and May 9, 2007, we randomly allocated 279 patients to receive conventional chemoradiotherapy, 280 to accelerated radiotherapy-chemotherapy, and 281 to very accelerated radiotherapy. Median follow-up was 5·2 years (IQR 4·9-6·2); rates of chemotherapy and radiotherapy compliance were good in all groups. Accelerated radiotherapy-chemotherapy offered no PFS benefit compared with conventional chemoradiotherapy (HR 1·02, 95% CI 0·84-1·23; p=0·88) or very accelerated radiotherapy (0·83, 0·69-1·01; p=0·060); conventional chemoradiotherapy improved PFS compared with very accelerated radiotherapy (0·82, 0·67-0·99; p=0·041). 3-year PFS was 37·6% (95% CI 32·1-43·4) after conventional chemoradiotherapy, 34·1% (28·7-39·8) after accelerated radiotherapy-chemotherapy, and 32·2% (27·0-37·9) after very accelerated radiotherapy. More patients in the very accelerated radiotherapy group had RTOG grade 3-4 acute mucosal toxicity (226 [84%] of 268 patients) compared with accelerated radiotherapy-chemotherapy (205 [76%] of 271 patients) or conventional chemoradiotherapy (180 [69%] of 262; p=0·0001). 158 (60%) of 265 patients in the conventional chemoradiotherapy group, 176 (64%) of 276 patients in the accelerated radiotherapy-chemotherapy group, and 190 (70%) of 272 patients in the very accelerated radiotherapy group were intubated with feeding tubes during treatment (p=0·045).
  
  
  CONCLUSIONS
  Chemotherapy has a substantial treatment effect given concomitantly with radiotherapy and acceleration of radiotherapy cannot compensate for the absence of chemotherapy. We noted the most favourable outcomes for conventional chemoradiotherapy, suggesting that acceleration of radiotherapy is probably not beneficial in concomitant chemoradiotherapy schedules.
  
  
  BACKGROUND
  French Ministry of Health.
authors.affiliation: Department of Radiation Oncology, Institut Gustave Roussy, Villejuif, France. bourhis@igr.fr
authors.forename: Jean
authors.initials: J
authors.lastname: Bourhis
authors.forename: Christian
authors.initials: C
authors.lastname: Sire
authors.forename: Pierre
authors.initials: P
authors.lastname: Graff
authors.forename: Vincent
authors.initials: V
authors.lastname: Grégoire
authors.forename: Philippe
authors.initials: P
authors.lastname: Maingon
authors.forename: Gilles
authors.initials: G
authors.lastname: Calais
authors.forename: Bernard
authors.initials: B
authors.lastname: Gery
authors.forename: Laurent
authors.initials: L
authors.lastname: Martin
authors.forename: Marc
authors.initials: M
authors.lastname: Alfonsi
authors.forename: Patrick
authors.initials: P
authors.lastname: Desprez
authors.forename: Thierry
authors.initials: T
authors.lastname: Pignon
authors.forename: Etienne
authors.initials: E
authors.lastname: Bardet
authors.forename: Michel
authors.initials: M
authors.lastname: Rives
authors.forename: Lionel
authors.initials: L
authors.lastname: Geoffrois
authors.forename: Nicolas
authors.initials: N
authors.lastname: Daly-Schveitzer
authors.forename: Sok
authors.initials: S
authors.lastname: Sen
authors.forename: Claude
authors.initials: C
authors.lastname: Tuchais
authors.forename: Olivier
authors.initials: O
authors.lastname: Dupuis
authors.forename: Stéphane
authors.initials: S
authors.lastname: Guerif
authors.forename: Michel
authors.initials: M
authors.lastname: Lapeyre
authors.forename: Véronique
authors.initials: V
authors.lastname: Favrel
authors.forename: Marc
authors.initials: M
authors.lastname: Hamoir
authors.forename: Antoine
authors.initials: A
authors.lastname: Lusinchi
authors.forename: Stéphane
authors.initials: S
authors.lastname: Temam
authors.forename: Antonella
authors.initials: A
authors.lastname: Pinna
authors.forename: Yun Gan
authors.initials: YG
authors.lastname: Tao
authors.forename: Pierre
authors.initials: P
authors.lastname: Blanchard
authors.forename: Anne
authors.initials: A
authors.lastname: Aupérin
mesh_terms: D000328:Adult; D000368:Aged; D002277:Carcinoma / Q000628:therapy*; D059248:Chemoradiotherapy / Q000379:methods*; D018572:Disease-Free Survival; D005260:Female; D006258:Head and Neck Neoplasms / Q000628:therapy*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D061214:Patient Safety; D016896:Treatment Outcome