title: Preliminary results of trial NPC-0501 evaluating the therapeutic gain by changing from concurrent-adjuvant to induction-concurrent chemoradiotherapy, changing from fluorouracil to capecitabine, and changing from conventional to accelerated radiotherapy fractionation in patients with locoregionally advanced nasopharyngeal carcinoma.
abstract: BACKGROUND
  A current recommendation for locoregionally advanced nasopharyngeal carcinoma (NPC) is conventional fractionated radiotherapy with concurrent cisplatin plus adjuvant cisplatin and fluorouracil (PF). In this randomized trial, the authors evaluated the potential therapeutic benefit from changing to an induction-concurrent chemotherapy sequence, replacing fluorouracil with oral capecitabine, and/or using accelerated rather than conventional radiotherapy fractionation.
  
  
  METHODS
  Patients with stage III through IVB, nonkeratinizing NPC were randomly allocated to 1 of 6 treatment arms. The protocol was amended in 2009 to permit confining randomization to the conventional fractionation arms. The primary endpoint was progression-free survival. Secondary endpoints included overall survival and safety.
  
  
  RESULTS
  In total, 803 patients were accrued, and 706 patients were randomly allocated to all 6 treatment arms. Comparisons of induction PF versus adjuvant PF did not indicate a significant improvement. Unadjusted comparisons of induction cisplatin and capecitabine (PX) versus adjuvant PF indicated a favorable trend in progression-free survival for the conventional fractionation arm (P = .045); analyses that were adjusted for other significant factors and fractionation reflected a significant reduction in the hazards of disease progression (hazard ratio [HR], 0.54; 95% confidence interval [CI], 0.36-0.80) and death (HR, 0.42; 95% CI, 0.25-0.70). Unadjusted comparisons of induction sequences versus adjuvant sequences did not reach statistical significance, but adjusted comparisons indicated favorable improvements by induction sequence. Comparisons of induction PX versus induction PF revealed fewer toxicities (neutropenia and electrolyte disturbance), unadjusted comparisons of efficacy were statistically insignificant, but adjusted analyses indicated that induction PX had a lower hazard of death (HR, 0.57; 95% CI, 0.34-0.97). Changing the fractionation from conventional to accelerated did not achieve any benefit but incurred higher toxicities (acute mucositis and dehydration).
  
  
  CONCLUSIONS
  Preliminary results indicate that the benefit of changing to an induction-concurrent sequence remains uncertain; replacing fluorouracil with oral capecitabine warrants further validation in view of its convenience, favorable toxicity profile, and favorable trends in efficacy; and accelerated fractionation is not recommended for patients with locoregionally advanced NPC who receive chemoradiotherapy.
authors.affiliation: Department of Clinical Oncology, Pamela Youde Nethersole Eastern Hospital, Hong Kong, China.
authors.forename: Anne W M
authors.initials: AW
authors.lastname: Lee
authors.forename: Roger K C
authors.initials: RK
authors.lastname: Ngan
authors.forename: Stewart Y
authors.initials: SY
authors.lastname: Tung
authors.forename: Ashley
authors.initials: A
authors.lastname: Cheng
authors.forename: Dora L W
authors.initials: DL
authors.lastname: Kwong
authors.forename: Tai-Xiang
authors.initials: TX
authors.lastname: Lu
authors.forename: Anthony T C
authors.initials: AT
authors.lastname: Chan
authors.forename: Lucy L K
authors.initials: LL
authors.lastname: Chan
authors.forename: Harry
authors.initials: H
authors.lastname: Yiu
authors.forename: Wai-Tong
authors.initials: WT
authors.lastname: Ng
authors.forename: Frank
authors.initials: F
authors.lastname: Wong
authors.forename: Kam-Tong
authors.initials: KT
authors.lastname: Yuen
authors.forename: Stephen
authors.initials: S
authors.lastname: Yau
authors.forename: Foon-Yiu
authors.initials: FY
authors.lastname: Cheung
authors.forename: Oscar S H
authors.initials: OS
authors.lastname: Chan
authors.forename: Horace
authors.initials: H
authors.lastname: Choi
authors.forename: Rick
authors.initials: R
authors.lastname: Chappell
mesh_terms: D000328:Adult; D000368:Aged; D000069287:Capecitabine; D002277:Carcinoma; D059186:Chemoradiotherapy, Adjuvant / Q000379:methods*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D019583:Dose Fractionation, Radiation; D005472:Fluorouracil / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives*; D006801:Humans; D060828:Induction Chemotherapy; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000473:pathology / Q000628:therapy*; D009364:Neoplasm Recurrence, Local / Q000473:pathology / Q000628:therapy*; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil
keywords: accelerated fractionation; capecitabine; chemoradiotherapy; nasopharyngeal carcinoma; randomized controlled trial