title: Preliminary results of a randomized study (NPC-9902 Trial) on therapeutic gain by concurrent chemotherapy and/or accelerated fractionation for locally advanced nasopharyngeal carcinoma.
abstract: OBJECTIVE
  To compare the benefit achieved by concurrent chemoradiotherapy (CRT) and/or accelerated fractionation (AF) vs. radiotherapy (RT) alone with conventional fractionation (CF) for patients with T3-4N0-1M0 nasopharyngeal carcinoma (NPC).
  
  
  METHODS
  All patients were irradiated with the same RT technique to > or =66 Gy at 2 Gy per fraction, conventional five fractions/week in the CF and CF+C (chemotherapy) arms, and accelerated six fractions/week in the AF and AF+C arms. The CF+C and AF+C patients were given the Intergroup 0099 regimen (concurrent cisplatin plus adjuvant cisplatin and 5-fluorouracil).
  
  
  RESULTS
  Between 1999 and April 2004, 189 patients were randomly assigned; the trial was terminated early because of slow accrual. The median follow-up was 2.9 years. When compared with the CF arm, significant improvement in failure-free survival (FFS) was achieved by the AF+C arm (94% vs. 70% at 3 years, p = 0.008), but both the AF arm and the CF+C arm were insignificant (p > or = 0.38). Multivariate analyses showed that CRT was a significant factor: hazard ratio (HR) = 0.52 (0.28-0.97), AF per se was insignificant: HR = 0.68 (0.37-1.25); the interaction of CRT by AF was strongly significant (p = 0.006). Both CRT arms had significant increase in acute toxicities (p < 0.005), and the AF+C arm also incurred borderline increase in late toxicities (34% vs. 14% at 3 years, p = 0.05).
  
  
  CONCLUSIONS
  Preliminary results suggest that concurrent chemoradiotherapy with accelerated fractionation could significantly improve tumor control when compared with conventional RT alone; further confirmation of therapeutic ratio is warranted.
authors.affiliation: Department of Clinical Oncology, Pamela Youde Nethersole Eastern Hospital, 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: Anthony T C
authors.initials: AT
authors.lastname: Chan
authors.forename: Rick
authors.initials: R
authors.lastname: Chappell
authors.forename: Yiu-Tong
authors.initials: YT
authors.lastname: Fu
authors.forename: Tai-Xiang
authors.initials: TX
authors.lastname: Lu
authors.forename: Terence
authors.initials: T
authors.lastname: Tan
authors.forename: Daniel T T
authors.initials: DT
authors.lastname: Chua
authors.forename: Brian
authors.initials: B
authors.lastname: O'sullivan
authors.forename: Shirley L
authors.initials: SL
authors.lastname: Xu
authors.forename: Ellie S Y
authors.initials: ES
authors.lastname: Pang
authors.forename: Wai-Man
authors.initials: WM
authors.lastname: Sze
authors.forename: To-Wai
authors.initials: TW
authors.lastname: Leung
authors.forename: Wing-Hong
authors.initials: WH
authors.lastname: Kwan
authors.forename: Paddy T M
authors.initials: PT
authors.lastname: Chan
authors.forename: Xiu-Fang
authors.initials: XF
authors.lastname: Liu
authors.forename: Eng-Huat
authors.initials: EH
authors.lastname: Tan
authors.forename: Jonathan S T
authors.initials: JS
authors.lastname: Sham
authors.forename: Lillian
authors.initials: L
authors.lastname: Siu
authors.forename: Wai-Hon
authors.initials: WH
authors.lastname: Lau
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy / Q000009:adverse effects / Q000379:methods; D019583:Dose Fractionation, Radiation; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D009367:Neoplasm Staging; D016896:Treatment Outcome
chemical_list: D002945:Cisplatin; D005472:Fluorouracil