Title: Gemcitabine and Cisplatin Induction Chemotherapy in Nasopharyngeal Carcinoma
Author: Yuan Zhang, Lei Chen, Guo-Qing Hu, Ning Zhang, Xiao-Dong Zhu, Kun-Yu Yang, Feng Jin, Mei Shi, Yu-Pei Chen, Wei-Han Hu, Zhi-Bin Cheng, Si-Yang Wang, Ye Tian, Xi-Cheng Wang, Yan Sun, Jin-Gao Li, Wen-Fei Li, Yu-Hong Li, Ling-Long Tang, Yan-Ping Mao, Guan-Qun Zhou, Rui Sun, Xu Liu, Rui Guo, Guo-Xian Long, Shao-Qiang Liang, Ling Li, Jing Huang, Jin-Hua Long, Jian Zang, Qiao-Dan Liu, Li Zou, Qiong-Fei Su, Bao-Min Zheng, Yun Xiao, Ying Guo, Fei Han, Hao-Yuan Mo, Jia-Wei Lv, Xiao-Jing Du, Cheng Xu, Na Liu, Ying-Qin Li, Melvin L. K. Chua, Fang-Yun Xie, Ying Sun, Jun Ma
Issue&Volume: Vol 381 No 12
Platinum-based concurrent chemoradiotherapy is the standard of care for patients with locoregionally advanced nasopharyngeal carcinoma. Additional gemcitabine and cisplatin induction chemotherapy has shown promising efficacy in phase 2 trials.
In a parallel-group, multicenter, randomized, controlled, phase 3 trial, we compared gemcitabine and cisplatin as induction chemotherapy plus concurrent chemoradiotherapy with concurrent chemoradiotherapy alone. Patients with locoregionally advanced nasopharyngeal carcinoma were randomly assigned in a 1:1 ratio to receive gemcitabine (at a dose of 1 g per square meter of body-surface area on days 1 and 8) plus cisplatin (80 mg per square meter on day 1), administered every 3 weeks for three cycles, plus chemoradiotherapy (concurrent cisplatin at a dose of 100 mg per square meter every 3 weeks for three cycles plus intensity-modulated radiotherapy) or chemoradiotherapy alone. The primary end point was recurrence-free survival (i.e., freedom from disease recurrence [distant metastasis or locoregional recurrence] or death from any cause) in the intention-to-treat population. Secondary end points included overall survival, treatment adherence, and safety.
A total of 480 patients were included in the trial (242 patients in the induction chemotherapy group and 238 in the standard-therapy group). At a median follow-up of 42.7 months, the 3-year recurrence-free survival was 85.3% in the induction chemotherapy group and 76.5% in the standard-therapy group (stratified hazard ratio for recurrence or death, 0.51; 95% confidence interval [CI], 0.34 to 0.77; P=0.001). Overall survival at 3 years was 94.6% and 90.3%, respectively (stratified hazard ratio for death, 0.43; 95% CI, 0.24 to 0.77). A total of 96.7% of the patients completed three cycles of induction chemotherapy. The incidence of acute adverse events of grade 3 or 4 was 75.7% in the induction chemotherapy group and 55.7% in the standard-therapy group, with a higher incidence of neutropenia, thrombocytopenia, anemia, nausea, and vomiting in the induction chemotherapy group. The incidence of grade 3 or 4 late toxic effects was 9.2% in the induction chemotherapy group and 11.4% in the standard-therapy group.
Induction chemotherapy added to chemoradiotherapy significantly improved recurrence-free survival and overall survival, as compared with chemoradiotherapy alone, among patients with locoregionally advanced nasopharyngeal carcinoma.