Li Zhang1, Yan Huang2, Shaodong Hong2, Yunpeng Yang2, Gengsheng Yu3, Jun Jia4, Peijian Peng5, Xuan Wu2, Qing Lin6, Xuping Xi7, Jiewen Peng8, Mingjun Xu9, Dongping Chen10, Xiaojun Lu11, Rensheng Wang12, Xiaolong Cao13, Xiaozhong Chen14, Zhixiong Lin15, Jianping Xiong16, Qin Lin17, Conghua Xie18, Zhihua Li19, Jianji Pan20, Jingao Li21, Shixiu Wu22, Yingni Lian23, Quanlie Yang24, Chong Zhao25. 1. 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. 2. 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. 3. Department of Medical Oncology, Jiangmen Central Hospital, Jiangmen, China. 4. Department of Medical Oncology, Dongguan People's Hospital, Dongguan, China. 5. Department of Medical Oncology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China. 6. Department of Oncology, Shunde Hospital of Traditional Chinese Medicine, Foshan, China. 7. Department of Radiotherapy, Cancer Hospital of Hunan Province, Changsha, China. 8. Department of Medical Oncology, Zhongshan People's Hospital, Zhongshan, China. 9. Department of Oncology, The First Affiliated Hospital of Gangnan Medical College, Gangnan, China. 10. Department of Radiotherapy, The Affiliated Cancer Hospital of Guangzhou Medical University, Guangzhou, China. 11. Department of Radiotherapy, Zhongshan People's Hospital, Zhongshan, China. 12. Department of Radiotherapy, The First Affiliated Hospital of Guangxi Medical University, Nanning, China. 13. Department of Oncology, Panyu Central Hospital, Guangzhou, China. 14. Department of Radiotherapy, Cancer Hospital of Zhejiang Province, Hangzhou, China. 15. Department of Medical Oncology, The Affiliated Cancer Hospital of Shantou University, Shantou, China. 16. Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, China. 17. Department of Radiotherapy, The First Affiliated Hospital of Xiamen University, Xiamen, China. 18. Department of Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China. 19. Department of Oncology, Sun Yat-sen Memorial Hospital, Guangzhou, China. 20. Department of Radiotherapy, Fujian Provincial Cancer Hospital, Fuzhou, China. 21. Department of Radiotherapy, Jiangxi Provincial Cancer Hospital, Nanchang, China. 22. Department of Radiotherapy, Cancer Hospital of Hangzhou City, Hangzhou, China. 23. Department of Medical Oncology, The First People's Hospital of Zhaoqing City, Zhaoqing, China. 24. Department of Chemotherapy, People's Hospital of Meizhou, Meizhou, China. 25. 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.
Abstract
BACKGROUND: 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. METHODS: 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/m2 intravenously on days 1 and 8) and cisplatin (80 mg/m2 intravenously on day 1), or fluorouracil (4 g/m2 in continuous intravenous infusion over 96 h) and cisplatin (80 mg/m2 on 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. FINDINGS: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 thegemcitabinegroup and 173 patients in thefluorouracil 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. INTERPRETATION: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. FUNDING: 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).
RCT Entities:
BACKGROUND: 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. METHODS: 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/m2 intravenously on days 1 and 8) and cisplatin (80 mg/m2 intravenously on day 1), or fluorouracil (4 g/m2 in continuous intravenous infusion over 96 h) and cisplatin (80 mg/m2 on 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. FINDINGS: 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. INTERPRETATION: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. FUNDING: 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: Christopher DeRenzo; Catherine Lam; Carlos Rodriguez-Galindo; Louis Rapkin; Stephen Gottschalk; Rajkumar Venkatramani Journal: Pediatr Blood Cancer Date: 2018-10-14 Impact factor: 3.167
Authors: Niha Beig; Kaustav Bera; Prateek Prasanna; Jacob Antunes; Ramon Correa; Salendra Singh; Anas Saeed Bamashmos; Marwa Ismail; Nathaniel Braman; Ruchika Verma; Virginia B Hill; Volodymyr Statsevych; Manmeet S Ahluwalia; Vinay Varadan; Anant Madabhushi; Pallavi Tiwari Journal: Clin Cancer Res Date: 2020-02-20 Impact factor: 12.531