title: Chemotherapy in locally advanced nasopharyngeal carcinoma: an individual patient data meta-analysis of eight randomized trials and 1753 patients.
abstract: OBJECTIVE
  To study the effect of adding chemotherapy to radiotherapy (RT) on overall survival and event-free survival for patients with nasopharyngeal carcinoma.
  
  
  METHODS
  This meta-analysis used updated individual patient data from randomized trials comparing chemotherapy plus RT with RT alone in locally advanced nasopharyngeal carcinoma. The log-rank test, stratified by trial, was used for comparisons, and the hazard ratios of death and failure 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 included 11 comparisons using the data from 1975 patients. The median follow-up was 6 years. The pooled hazard ratio of death was 0.82 (95% confidence interval, 0.71-0.94; p = 0.006), corresponding to an absolute survival benefit of 6% at 5 years from the addition of chemotherapy (from 56% to 62%). The pooled hazard ratio of tumor failure or death was 0.76 (95% confidence interval, 0.67-0.86; p < 0.0001), corresponding to an absolute event-free survival benefit of 10% at 5 years from the addition of chemotherapy (from 42% to 52%). A significant interaction was observed between the timing of chemotherapy and overall survival (p = 0.005), explaining the heterogeneity observed in the treatment effect (p = 0.03), with the highest benefit resulting 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 RT.
authors.affiliation: Institut Gustave-Roussy, Villejuif, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Baujat
authors.forename: Hélène
authors.initials: H
authors.lastname: Audry
authors.forename: Jean
authors.initials: J
authors.lastname: Bourhis
authors.forename: Anthony T C
authors.initials: AT
authors.lastname: Chan
authors.forename: Haluk
authors.initials: H
authors.lastname: Onat
authors.forename: Daniel T T
authors.initials: DT
authors.lastname: Chua
authors.forename: Dora L W
authors.initials: DL
authors.lastname: Kwong
authors.forename: Muhyi
authors.initials: M
authors.lastname: Al-Sarraf
authors.forename: Kwan-Hwa
authors.initials: KH
authors.lastname: Chi
authors.forename: Masato
authors.initials: M
authors.lastname: Hareyama
authors.forename: Sing F
authors.initials: SF
authors.lastname: Leung
authors.forename: Kullathorn
authors.initials: K
authors.lastname: Thephamongkhol
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Pignon
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D003131:Combined Modality Therapy; D016001:Confidence Intervals; D006801:Humans; D016014:Linear Models; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy*; D016032:Randomized Controlled Trials as Topic
chemical_list: D000970:Antineoplastic Agents