title: Randomized trial of radiotherapy versus concurrent chemoradiotherapy followed by adjuvant chemotherapy in patients with American Joint Committee on Cancer/International Union against cancer stage III and IV nasopharyngeal cancer of the endemic variety.
abstract: OBJECTIVE
  The Intergroup 00-99 Trial for nasopharyngeal cancer (NPC) showed a benefit of adding chemotherapy to radiotherapy. However, there were controversies regarding the applicability of the results to patients in endemic regions. This study aims to confirm the findings of the 00-99 Trial and its applicability to patients with endemic NPC.
  
  
  METHODS
  Between September 1997 and May 2003, 221 patients were randomly assigned to receive radiotherapy (RT) alone (n = 110) or chemoradiotherapy (CRT; n = 111). Patients in both arms received 70 Gy in 7 weeks using standard RT portals and techniques. Patients on CRT received concurrent cisplatin (25 mg/m2 on days 1 to 4) on weeks 1, 4, and 7 of RT and adjuvant cisplatin (20 mg/m2 on days 1 to 4) and fluorouracil (1,000 mg/m2 on days 1 to 4) every 4 weeks (weeks 11, 15, and 19) for three cycles after completion of RT. All patients were analyzed by intent-to-treat analysis. The median follow-up time was 3.2 years.
  
  
  RESULTS
  Distant metastasis occurred in 38 patients on RT alone and 18 patients on CRT. The difference in 2-year cumulative incidence was 17% (95% CI, 14% to 20%; P = .0029). The hazard ratio (HR) for disease-free survival was 0.57 (95% CI, 0.38 to 0.87; P = .0093). The 2- and 3-year overall survival (OS) rates were 78% and 85% and 65% and 80% for RT alone and CRT, respectively. The HR for OS was 0.51 (95% CI, 0.31 to 0.81; P = .0061).
  
  
  CONCLUSIONS
  This report confirms the findings of the Intergroup 00-99 Trial and demonstrates its applicability to endemic NPC. This study also confirms that chemotherapy improves the distant metastasis control rate in NPC.
authors.affiliation: Department of Radiation Oncology, National Cancer Center, Singapore 169610, Republic of Singapore. trdwts@nccs.com.sg
authors.forename: Joseph
authors.initials: J
authors.lastname: Wee
authors.forename: Eng Huat
authors.initials: EH
authors.lastname: Tan
authors.forename: Bee Choo
authors.initials: BC
authors.lastname: Tai
authors.forename: Hwee Bee
authors.initials: HB
authors.lastname: Wong
authors.forename: Swan Swan
authors.initials: SS
authors.lastname: Leong
authors.forename: Terence
authors.initials: T
authors.lastname: Tan
authors.forename: Eu Tiong
authors.initials: ET
authors.lastname: Chua
authors.forename: Edward
authors.initials: E
authors.lastname: Yang
authors.forename: Khai Mun
authors.initials: KM
authors.lastname: Lee
authors.forename: Kam Weng
authors.initials: KW
authors.lastname: Fong
authors.forename: Hoon Seng Khoo
authors.initials: HS
authors.lastname: Tan
authors.forename: Kim Shang
authors.initials: KS
authors.lastname: Lee
authors.forename: Susan
authors.initials: S
authors.lastname: Loong
authors.forename: Vijay
authors.initials: V
authors.lastname: Sethi
authors.forename: Eu Jin
authors.initials: EJ
authors.lastname: Chua
authors.forename: David
authors.initials: D
authors.lastname: Machin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D019353:Endemic Diseases; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000453:epidemiology* / Q000473:pathology / Q000628:therapy*; D009367:Neoplasm Staging; D011336:Probability; D016016:Proportional Hazards Models; D011879:Radiotherapy Dosage; D018714:Radiotherapy, Adjuvant; D012016:Reference Values; D018570:Risk Assessment; D012846:Singapore / Q000453:epidemiology; D016019:Survival Analysis; D016896:Treatment Outcome