title: Gemcitabine plus cisplatin versus fluorouracil plus cisplatin in recurrent or metastatic nasopharyngeal carcinoma: a multicentre, randomised, open-label, phase 3 trial.
abstract: Outcomes are poor for patients with recurrent or metastatic nasopharyngeal carcinoma and no well established first-line chemotherapy is available for the disease. We compared the efficacy and safety of gemcitabine plus cisplatin versus fluorouracil plus cisplatin in patients with recurrent or metastatic nasopharyngeal carcinoma.
  
  
  
  In this multicentre, randomised, open-label, phase 3 trial, patients with recurrent or metastatic nasopharyngeal carcinoma were recruited from 22 hospitals in China. Key inclusion criteria were Eastern Cooperative Oncology Group performance status of 0 or 1, adequate organ function, and measurable lesions according to Response Evaluation Criteria in Solid Tumors version 1.1. Patients were randomly assigned in a 1:1 ratio to receive either gemcitabine (1 g/m2intravenously on days 1 and 8) and cisplatin (80 mg/m2intravenously on day 1), or fluorouracil (4 g/m2in continuous intravenous infusion over 96 h) and cisplatin (80 mg/m2on day 1 given intravenously) once every 3 weeks for a maximum of six cycles. The randomisation was done centrally via an interactive phone response system using block randomisation with a size of six. The primary endpoint was progression-free survival assessed by the independent image committee in the intention-to-treat population. Safety analyses were done in patients who received at least one cycle of study drug. This study is ongoing and is registered with ClinicalTrials.gov, number NCT01528618.
  
  
  
  Between Feb 20, 2012, and Oct 30, 2015, 362 patients were randomly assigned to a group (181 to the gemcitabine [plus cisplatin] group and 181 to the fluorouracil [plus cisplatin] group). Median follow-up time for progression-free survival was 19·4 months (IQR 12·1-35·6). The median progression-free survival was 7·0 months (4·4-10·9) in the gemcitabine group and 5·6 months (3·0-7·0) in the fluorouracil group (hazard ratio [HR] 0·55 [95% CI 0·44-0·68]; p<0·0001). A total of 180 patients in the gemcitabine group and 173 patients in the fluorouracil group were included in the safety analysis. Significantly different treatment-related grade 3 or 4 adverse events between the gemcitabine and fluorouracil groups were leucopenia (52 [29%] vs 15 [9%]; <0·0001), neutropenia (41 [23%] vs 23 [13%]; p=0·0251), thrombocytopenia (24 [13%] vs three [2%]; p=0·0007), and mucosal inflammation (0 vs 25 [14%]; <0·0001). Serious treatment-related adverse events occurred in seven (4%) patients in the gemcitabine group and ten (6%) in the fluorouracil group. Six (3%) patients in the gemcitabine group and 14 (8%) patients in the fluorouracil group discontinued treatment because of drug-related adverse events. No treatment-related deaths occurred in either group.
  
  
  
  Gemcitabine plus cisplatin prolongs progression-free survival in patients with recurrent or metastatic nasopharyngeal carcinoma. The results establish gemcitabine plus cisplatin as the standard first-line treatment option for this population.
  
  
  
  Sun Yat-Sen University Clinical Research 5010 Programme, Chinese National Natural Science Foundation project (grant numbers 81372502 and 81201917), the National High Technology Research and Development Program of China (863 program numbers 2012AA02A501 and 2012AA02A502), and the Natural Science Foundation of Guangdong (grant number S2013010016564).
authors: Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. Electronic address: zhangli6@mail.sysu.edu.cn.
authors: Li
authors: L
authors: Zhang
authors: Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors: Yan
authors: Y
authors: Huang
authors: Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors: Shaodong
authors: S
authors: Hong
authors: Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors: Yunpeng
authors: Y
authors: Yang
authors: Department of Medical Oncology, Jiangmen Central Hospital, Jiangmen, China.
authors: Gengsheng
authors: G
authors: Yu
authors: Department of Medical Oncology, Dongguan People's Hospital, Dongguan, China.
authors: Jun
authors: J
authors: Jia
authors: Department of Medical Oncology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China.
authors: Peijian
authors: P
authors: Peng
authors: Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors: Xuan
authors: X
authors: Wu
authors: Department of Oncology, Shunde Hospital of Traditional Chinese Medicine, Foshan, China.
authors: Qing
authors: Q
authors: Lin
authors: Department of Radiotherapy, Cancer Hospital of Hunan Province, Changsha, China.
authors: Xuping
authors: X
authors: Xi
authors: Department of Medical Oncology, Zhongshan People's Hospital, Zhongshan, China.
authors: Jiewen
authors: J
authors: Peng
authors: Department of Oncology, The First Affiliated Hospital of Gangnan Medical College, Gangnan, China.
authors: Mingjun
authors: M
authors: Xu
authors: Department of Radiotherapy, The Affiliated Cancer Hospital of Guangzhou Medical University, Guangzhou, China.
authors: Dongping
authors: D
authors: Chen
authors: Department of Radiotherapy, Zhongshan People's Hospital, Zhongshan, China.
authors: Xiaojun
authors: X
authors: Lu
authors: Department of Radiotherapy, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
authors: Rensheng
authors: R
authors: Wang
authors: Department of Oncology, Panyu Central Hospital, Guangzhou, China.
authors: Xiaolong
authors: X
authors: Cao
authors: Department of Radiotherapy, Cancer Hospital of Zhejiang Province, Hangzhou, China.
authors: Xiaozhong
authors: X
authors: Chen
authors: Department of Medical Oncology, The Affiliated Cancer Hospital of Shantou University, Shantou, China.
authors: Zhixiong
authors: Z
authors: Lin
authors: Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, China.
authors: Jianping
authors: J
authors: Xiong
authors: Department of Radiotherapy, The First Affiliated Hospital of Xiamen University, Xiamen, China.
authors: Qin
authors: Q
authors: Lin
authors: Department of Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China.
authors: Conghua
authors: C
authors: Xie
authors: Department of Oncology, Sun Yat-sen Memorial Hospital, Guangzhou, China.
authors: Zhihua
authors: Z
authors: Li
authors: Department of Radiotherapy, Fujian Provincial Cancer Hospital, Fuzhou, China.
authors: Jianji
authors: J
authors: Pan
authors: Department of Radiotherapy, Jiangxi Provincial Cancer Hospital, Nanchang, China.
authors: Jingao
authors: J
authors: Li
authors: Department of Radiotherapy, Cancer Hospital of Hangzhou City, Hangzhou, China.
authors: Shixiu
authors: S
authors: Wu
authors: Department of Medical Oncology, The First People's Hospital of Zhaoqing City, Zhaoqing, China.
authors: Yingni
authors: Y
authors: Lian
authors: Department of Chemotherapy, People's Hospital of Meizhou, Meizhou, China.
authors: Quanlie
authors: Q
authors: Yang
authors: Department of Radiotherapy, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors: Chong
authors: C
authors: Zhao
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002277:Carcinoma; D002681:China; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy / Q000556:secondary; D008297:Male; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D016017:Odds Ratio; D018579:Patient Selection; D012307:Risk Factors; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D002945:Cisplatin; D005472:Fluorouracil; D000093542:Gemcitabine