title: Randomized trial of radiotherapy plus concurrent-adjuvant chemotherapy vs radiotherapy alone for regionally advanced nasopharyngeal carcinoma.
abstract: BACKGROUND
  Current practice of adding concurrent-adjuvant chemotherapy to radiotherapy (CRT) for treating advanced nasopharyngeal carcinoma is based on the Intergroup-0099 Study published in 1998. However, the outcome for the radiotherapy-alone (RT) group in that trial was substantially poorer than those in other trials, and there were no data on late toxicities. Verification of the long-term therapeutic index of this regimen is needed.
  
  
  METHODS
  Patients with nonkeratinizing nasopharyngeal carcinoma staged T1-4N2-3M0 were randomly assigned to RT (176 patients) or to CRT (172 patients) using cisplatin (100 mg/m(2)) every 3 weeks for three cycles in concurrence with radiotherapy, followed by cisplatin (80 mg/m(2)) plus fluorouracil (1000 mg per m(2) per day for 4 days) every 4 weeks for three cycles. Primary endpoints included overall failure-free rate (FFR) (the time to first failure at any site) and progression-free survival. Secondary endpoints included overall survival, locoregional FFR, distant FFR, and acute and late toxicity rates. All statistical tests were two-sided.
  
  
  RESULTS
  The two treatment groups were well balanced in all patient characteristics, tumor factors, and radiotherapy parameters. Adding chemotherapy statistically significantly improved the 5-year FFR (CRT vs RT: 67% vs 55%; P = .014) and 5-year progression-free survival (CRT vs RT: 62% vs 53%; P = .035). Cumulative incidence of acute toxicity increased with chemotherapy by 30% (CRT vs RT: 83% vs 53%; P < .001), but the 5-year late toxicity rate did not increase statistically significantly (CRT vs RT: 30% vs 24%; P = .30). Deaths because of disease progression were reduced statistically significantly by 14% (CRT vs RT: 38% vs 24%; P = .008), but 5-year overall survival was similar (CRT vs RT: 68% vs 64%; P = .22; hazard ratio of CRT = 0.81, 95% confidence interval = 0.58 to 1.13) because deaths due to toxicity or incidental causes increased by 7% (CRT vs RT: 1.7% vs 0, and 8.1% vs 3.4%, respectively; P = .015).
  
  
  CONCLUSIONS
  Adding concurrent-adjuvant chemotherapy statistically significantly reduced failure and cancer-specific deaths when compared with radiotherapy alone. Although there was no statistically significant increase in major late toxicity, increase in noncancer deaths narrowed the resultant gain in overall survival.
authors.affiliation: Department of Clinical Oncology, Pamela Youde Nethersole Eastern Hospital, Chai Wan, Hong Kong, China. awmlee@ha.org.hk
authors.forename: Anne W M
authors.initials: AW
authors.lastname: Lee
authors.forename: Stewart Y
authors.initials: SY
authors.lastname: Tung
authors.forename: Daniel T T
authors.initials: DT
authors.lastname: Chua
authors.forename: Roger K C
authors.initials: RK
authors.lastname: Ngan
authors.forename: Rick
authors.initials: R
authors.lastname: Chappell
authors.forename: Raymond
authors.initials: R
authors.lastname: Tung
authors.forename: Lillian
authors.initials: L
authors.lastname: Siu
authors.forename: W T
authors.initials: WT
authors.lastname: Ng
authors.forename: W K
authors.initials: WK
authors.lastname: Sze
authors.forename: Gordon K H
authors.initials: GK
authors.lastname: Au
authors.forename: Stephen C K
authors.initials: SC
authors.lastname: Law
authors.forename: Brian
authors.initials: B
authors.lastname: O'Sullivan
authors.forename: T K
authors.initials: TK
authors.lastname: Yau
authors.forename: T W
authors.initials: TW
authors.lastname: Leung
authors.forename: Joseph S K
authors.initials: JS
authors.lastname: Au
authors.forename: W M
authors.initials: WM
authors.lastname: Sze
authors.forename: C W
authors.initials: CW
authors.lastname: Choi
authors.forename: K K
authors.initials: KK
authors.lastname: Fung
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Lau
authors.forename: W H
authors.initials: WH
authors.lastname: Lau
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006723:Hong Kong / Q000453:epidemiology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D016609:Neoplasms, Second Primary / Q000453:epidemiology / Q000209:etiology; D016017:Odds Ratio; D018714:Radiotherapy, Adjuvant; D013405:Suicide / Q000706:statistics & numerical data; D016896:Treatment Outcome
chemical_list: D002945:Cisplatin; D005472:Fluorouracil