title: Concurrent chemoradiotherapy plus adjuvant chemotherapy versus concurrent chemoradiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma: a phase 3 multicentre randomised controlled trial.
abstract: BACKGROUND
  The effect of the addition of adjuvant chemotherapy to concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma is unclear. We aimed to assess the contribution of adjuvant chemotherapy to concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone.
  
  
  METHODS
  We did an open-label phase 3 multicentre randomised controlled trial at seven institutions in China. Randomisation was by a computer-generated random number code. Patients were stratified by treatment centre and randomly assigned in blocks of four. Treatment allocation was not masked. We randomly assigned patients with non-metastatic stage III or IV (except T3-4N0) nasopharyngeal carcinoma to receive concurrent chemoradiotherapy plus adjuvant chemotherapy or concurrent chemoradiotherapy alone. Patients in both groups received 40 mg/m(2) cisplatin weekly up to 7 weeks, concurrently with radiotherapy. Radiotherapy was given as 2·0-2·27 Gy per fraction with five daily fractions per week for 6-7 weeks to a total dose of 66 Gy or greater to the primary tumour and 60-66 Gy to the involved neck area. The concurrent chemoradiotherapy plus adjuvant chemotherapy group subsequently received 80 mg/m(2) adjuvant cisplatin and 800 mg/m(2) per day fluorouracil for 120 h every 4 weeks for three cycles. Our primary endpoint was failure-free survival. We did efficacy analyses in our intention-to-treat population. Our trial is ongoing; in this report we present the 2 year survival results and acute toxic effects. This trial is registered with ClinicalTrials.gov, number NCT00677118.
  
  
  RESULTS
  251 patients were assigned to the concurrent chemoradiotherapy plus adjuvant chemotherapy group and 257 to the concurrent chemoradiotherapy alone group. After a median follow-up of 37·8 months (range 1·3-61·0), the estimated 2 year failure-free survival rate was 86% (95% CI 81-90) in the concurrent chemoradiotherapy plus adjuvant chemotherapy group and 84% (78-88) in concurrent chemoradiotherapy only group (hazard ratio 0·74, 95% CI 0·49-1·10; p=0·13). Stomatitis was the most commonly reported grade 3 or 4 adverse event during both radiotherapy (76 of 249 patients in the concurrent chemoradiotherapy plus adjuvant chemotherapy group and 82 of 254 in the concurrent chemoradiotherapy alone group) and adjuvant chemotherapy (43 [21%] of 205 patients treated with adjuvant chemotherapy).
  
  
  CONCLUSIONS
  Adjuvant cisplatin and fluorouracil chemotherapy did not significantly improve failure-free survival after concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma. Longer follow-up is needed to fully assess survival and late toxic effects, but such regimens should not, at present, be used outside well-designed clinical trials.
  
  
  BACKGROUND
  Sun Yat-sen University Clinical Research 5010 Programme (No 2007037), Science Foundation of Key Hospital Clinical Programme of Ministry of Health PR China (No 2010-178), and Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme (2010).
authors.affiliation: State Key Laboratory of Oncology in South China, Department of Radiation Oncology, Sun Yat-sen University Cancer Centre, Guangzhou, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.forename: Chao-Su
authors.initials: CS
authors.lastname: Hu
authors.forename: Xiao-Zhong
authors.initials: XZ
authors.lastname: Chen
authors.forename: Guo-Qing
authors.initials: GQ
authors.lastname: Hu
authors.forename: Zhi-Bin
authors.initials: ZB
authors.lastname: Cheng
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.forename: Wei-Xiong
authors.initials: WX
authors.lastname: Li
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Chen
authors.forename: Fang-Yun
authors.initials: FY
authors.lastname: Xie
authors.forename: Shao-Bo
authors.initials: SB
authors.lastname: Liang
authors.forename: Yong
authors.initials: Y
authors.lastname: Chen
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Xu
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.forename: Guo-Xian
authors.initials: GX
authors.lastname: Long
authors.forename: Si-Yang
authors.initials: SY
authors.lastname: Wang
authors.forename: Bao-Min
authors.initials: BM
authors.lastname: Zheng
authors.forename: Ying
authors.initials: Y
authors.lastname: Guo
authors.forename: Ying
authors.initials: Y
authors.lastname: Sun
authors.forename: Yan-Ping
authors.initials: YP
authors.lastname: Mao
authors.forename: Ling-Long
authors.initials: LL
authors.lastname: Tang
authors.forename: Yu-Ming
authors.initials: YM
authors.lastname: Chen
authors.forename: Meng-Zhong
authors.initials: MZ
authors.lastname: Liu
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols; D002277:Carcinoma; D059248:Chemoradiotherapy / Q000379:methods*; D017024:Chemotherapy, Adjuvant / Q000379:methods*; D002681:China; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000453:epidemiology* / Q000628:therapy*; D009367:Neoplasm Staging; D055815:Young Adult
chemical_list: D002945:Cisplatin; D005472:Fluorouracil