title: Induction chemotherapy followed by concurrent radio-chemotherapy versus concurrent radio-chemotherapy alone as treatment of locally advanced squamous cell carcinoma of the head and neck (HNSCC): A meta-analysis of randomized trials.
abstract: BACKGROUND
  Induction chemotherapy with docetaxel, cisplatin and 5 FU (TPF) before radiotherapy (RT) or radio-chemotherapy (RT-CHX) has been shown to improve overall survival (OS) compared to induction chemotherapy with cisplatin and 5 FU in locally advanced squamous cell carcinoma of the head and neck (HNSCC). Whether TPF induction before RT-CHX improves clinical outcome in comparison with RT-CHX alone is still a matter of debate. Recently, the results of 5 randomized trials addressing this question have become available.
  
  
  METHODS
  In the 5 trials of interest, in total 1022 patients with locally advanced HNSCC were randomly assigned to receive either TPF induction CHX followed by concurrent RT-CHX or concurrent RT-CHX alone. Platin or taxane based CHX was used during RT. 51.3% of the patients had oropharyngeal, 7.3% hypoharyngeal, 18.7% laryngeal, 19.4% oral cavity and 3.5% had other HNSCC. Published hazard ratios and hazard ratios extracted from available survival curves for OS and progression free survival (PFS) were basis of the meta-analysis. Meta-analysis of the effect sizes on OS and PFS was performed using a random effects model based on parameter estimates of log hazard ratios in Cox models and their standard errors.
  
  
  RESULTS
  Additional induction CHX with TPF before RT-CHX did neither result in a significant improvement of OS (Hazard Ratio: 1.010, 95% confidence limits (CL) 0.84-1.21, p=0.92), nor in a statistically significant benefit of PFS (Hazard Ratio: 0.91, 95% CL 0.75-1.1, p=0.32).
  
  
  CONCLUSIONS
  Additional induction CHX with TPF before RT-CHX does not improve OS and PFS in locally advanced HNSCC compared to definite RT-CHX.
authors.affiliation: Medical Faculty, Department of Radiation Oncology, Heinrich Heine University, Dusseldorf, Germany.
authors.forename: Wilfried
authors.initials: W
authors.lastname: Budach
authors.affiliation: Medical Faculty, Department of Radiation Oncology, Heinrich Heine University, Dusseldorf, Germany.
authors.forename: Edwin
authors.initials: E
authors.lastname: Bölke
authors.affiliation: Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, USA.
authors.forename: Kai
authors.initials: K
authors.lastname: Kammers
authors.affiliation: Medical Faculty, Department of Dermatology, Heinrich Heine University, Dusseldorf, Germany.
authors.forename: Peter Arne
authors.initials: PA
authors.lastname: Gerber
authors.affiliation: Medical Faculty, Department of General, Visceral, and Thoracic Surgery, Asklepios Harz Hospitals, Goslar, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Orth
authors.affiliation: Medical Faculty, Department of Radiation Oncology, Heinrich Heine University, Dusseldorf, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Gripp
authors.affiliation: Medical Faculty, Department of Radiation Oncology, Heinrich Heine University, Dusseldorf, Germany. Electronic address: matuschek@med.uni-duesseldorf.de.
authors.forename: Christiane
authors.initials: C
authors.lastname: Matuschek
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000628:therapy*; D059248:Chemoradiotherapy / Q000379:methods*; D002945:Cisplatin / Q000627:therapeutic use; D018572:Disease-Free Survival; D000077143:Docetaxel; D005472:Fluorouracil / Q000627:therapeutic use; D006258:Head and Neck Neoplasms / Q000628:therapy*; D006801:Humans; D060828:Induction Chemotherapy / Q000379:methods*; D008297:Male; D016032:Randomized Controlled Trials as Topic; D000077195:Squamous Cell Carcinoma of Head and Neck; D043823:Taxoids / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D043823:Taxoids; D000077143:Docetaxel; D002945:Cisplatin; D005472:Fluorouracil
keywords: Head and neck cancer; Induction chemotherapy; Meta-analysis; Radiotherapy; Squamous cell carcinoma of the head and neck; TPF