title: Chemotherapy as an adjunct to radiotherapy in locally advanced nasopharyngeal carcinoma.
abstract: BACKGROUND
  A previous meta-analysis investigated the role of chemotherapy in head and neck locally advanced carcinoma. This work had not been performed on nasopharyngeal carcinoma.
  
  
  OBJECTIVE
  The aim of the project was to study the effect of adding chemotherapy to radiotherapy on overall survival (OS) and event-free survival (EFS) in patients with nasopharyngeal carcinoma.
  
  
  METHODS
  We searched MEDLINE (1966 to October 2003), EMBASE (1980 to October 2003) and the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 3, 2003) and trial registers. Handsearches of meeting abstracts, references in review articles and of the Chinese medical literature were carried out. Experts and pharmaceutical companies were asked to identify trials.
  
  
  METHODS
  Randomised trials comparing chemotherapy plus radiotherapy to radiotherapy alone in locally advanced nasopharyngeal carcinoma were included.
  
  
  METHODS
  The meta-analysis was based on updated individual patient data. The log rank test, stratified by trial, was used for comparisons and the hazard ratios (HR) of death and failure (loco-regional/distant failure or death) were calculated.
  
  
  RESULTS
  Eight trials with 1753 patients were included. One trial with a 2 x 2 design was counted twice in the analysis. The analysis was performed including 11 comparisons based on 1975 patients. The median follow up was six years. The pooled hazard ratio of death was 0.82 (95% confidence interval (CI) 0.71 to 0.95; P = 0.006) corresponding to an absolute survival benefit of 6% at five years from chemotherapy (from 56% to 62%). The pooled hazard ratio of tumour failure or death was 0.76 (95% CI 0.67 to 0.86; P < 0.00001) corresponding to an absolute event-free survival benefit of 10% at five years from chemotherapy (from 42% to 52%). A significant interaction was observed between chemotherapy timings and overall survival (P = 0.005), explaining the heterogeneity observed in the treatment effect (P = 0.03) with the highest benefit from concomitant chemotherapy.
  
  
  CONCLUSIONS
  Chemotherapy led to a small but significant benefit for overall survival and event-free survival. This benefit was essentially observed when chemotherapy was administered concomitantly with radiotherapy.
authors.affiliation: Hôpital Foch, Head and Neck Surgery, 40 rue Worth, Suresnes, France. b.baujat@hopital-foch.org
authors.forename: B
authors.initials: B
authors.lastname: Baujat
authors.forename: H
authors.initials: H
authors.lastname: Audry
authors.forename: J
authors.initials: J
authors.lastname: Bourhis
authors.forename: A T C
authors.initials: AT
authors.lastname: Chan
authors.forename: H
authors.initials: H
authors.lastname: Onat
authors.forename: D T T
authors.initials: DT
authors.lastname: Chua
authors.forename: D L W
authors.initials: DL
authors.lastname: Kwong
authors.forename: M
authors.initials: M
authors.lastname: Al-Sarraf
authors.forename: K H
authors.initials: KH
authors.lastname: Chi
authors.forename: M
authors.initials: M
authors.lastname: Hareyama
authors.forename: S F
authors.initials: SF
authors.lastname: Leung
authors.forename: K
authors.initials: K
authors.lastname: Thephamongkhol
authors.forename: J P
authors.initials: JP
authors.lastname: Pignon
mesh_terms: D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D006801:Humans; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy; D016032:Randomized Controlled Trials as Topic