Su-Mei Cao1, Qi Yang2, Ling Guo2, Hai-Qiang Mai2, Hao-Yuan Mo2, Ka-Jia Cao2, Chao-Nan Qian2, Chong Zhao2, Yan-Qun Xiang2, Xiu-Ping Zhang3, Zhi-Xiong Lin4, Wei-Xiong Li5, Qing Liu1, Fang Qiu2, Rui Sun2, Qiu-Yan Chen2, Pei-Yu Huang2, Dong-Hua Luo2, Yi-Jun Hua2, Yi-Shan Wu2, Xing Lv2, Lin Wang2, Wei-Xiong Xia2, Lin-Quan Tang2, Yan-Fang Ye1, Ming-Yuan Chen6, Xiang Guo7, Ming-Huang Hong8. 1. State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China; Department of Cancer Prevention Center, Sun Yat-sen University Cancer Center, Guangzhou, China. 2. State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China; Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, China. 3. Department of Radiation Oncology, Cancer Center of Guangzhou Medical University, Guangzhou, China. 4. Department of Radiation Oncology, Cancer Center of Shantou University Medical College, Shantou, China. 5. Department of Radiation Oncology, Guangdong General Hospital, Guangzhou, China. 6. State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China; Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, China. Electronic address: chmingy@mail.sysu.edu.cn. 7. State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China; Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, China. Electronic address: guoxiang@sysucc.org.cn. 8. State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China; Department of Clinical Trial Center, Sun Yat-sen University Cancer Center, Guangzhou, China. Electronic address: hongmh@sysucc.org.cn.
Abstract
BACKGROUND: The role of neoadjuvant chemotherapy (NACT) for locoregionally advanced nasopharyngeal carcinoma (NPC) is unclear. We aimed to evaluate the feasibility and efficacy of NACT followed by concurrent chemoradiotherapy (CCRT) versus CCRT alone in locoregionally advanced NPC. METHODS:Patients with stage III-IVB (excluding T3N0-1) NPC were randomly assigned to receive NACT followed by CCRT (investigational arm) or CCRT alone (control arm). Both arms were treated with 80 mg/m2 cisplatin every 3 weeks concurrently with radiotherapy. The investigational arm received cisplatin (80 mg/m2 d1) and fluorouracil (800 mg/m2 civ d1-5) every 3 weeks for two cycles before CCRT. The primary end-point was disease-free survival (DFS) and distant metastasis-free survival (DMFS). Secondary end-point was overall survival (OS). Survival curves for the time-to-event endpoints were analyzed by the Kaplan-Meier method and compared using the log-rank test. The P value was calculated using the 5-year endpoints. RESULTS:Four hundred seventy six patients were randomly assigned to the investigational (n = 238) and control arms (n = 238). The investigational arm achieved higher 3-year DFS rate (82.0%, 95% CI = 0.77-0.87) than the control arm (74.1%, 95% CI = 0.68-0.80, P = 0.028). The 3-year DMFS rate was 86.0% for the investigational arm versus 82.0% for the control arm, with marginal statistical significance (P = 0.056). However, there were no statistically significant differences in OS or locoregional relapse-free survival (LRRFS) rates between two arms (OS: 88.2% versus 88.5%, P = 0.815; LRRFS: 94.3% versus 90.8%, P = 0.430). The most common grade 3-4 toxicity during NACT was neutropenia (16.0%). During CCRT, the investigational arm experienced statistically significantly more grade 3-4 toxicities (P < 0.001). CONCLUSION:NACT improved tumour control compared with CCRT alone in locoregionally advanced NPC, particularly at distant sites. However, there was no early gain in OS. Longer follow-up is needed to determine the eventual therapeutic efficacy.
RCT Entities:
BACKGROUND: The role of neoadjuvant chemotherapy (NACT) for locoregionally advanced nasopharyngeal carcinoma (NPC) is unclear. We aimed to evaluate the feasibility and efficacy of NACT followed by concurrent chemoradiotherapy (CCRT) versus CCRT alone in locoregionally advanced NPC. METHODS:Patients with stage III-IVB (excluding T3N0-1) NPC were randomly assigned to receive NACT followed by CCRT (investigational arm) or CCRT alone (control arm). Both arms were treated with 80 mg/m2 cisplatin every 3 weeks concurrently with radiotherapy. The investigational arm received cisplatin (80 mg/m2 d1) and fluorouracil (800 mg/m2 civ d1-5) every 3 weeks for two cycles before CCRT. The primary end-point was disease-free survival (DFS) and distant metastasis-free survival (DMFS). Secondary end-point was overall survival (OS). Survival curves for the time-to-event endpoints were analyzed by the Kaplan-Meier method and compared using the log-rank test. The P value was calculated using the 5-year endpoints. RESULTS: Four hundred seventy six patients were randomly assigned to the investigational (n = 238) and control arms (n = 238). The investigational arm achieved higher 3-year DFS rate (82.0%, 95% CI = 0.77-0.87) than the control arm (74.1%, 95% CI = 0.68-0.80, P = 0.028). The 3-year DMFS rate was 86.0% for the investigational arm versus 82.0% for the control arm, with marginal statistical significance (P = 0.056). However, there were no statistically significant differences in OS or locoregional relapse-free survival (LRRFS) rates between two arms (OS: 88.2% versus 88.5%, P = 0.815; LRRFS: 94.3% versus 90.8%, P = 0.430). The most common grade 3-4 toxicity during NACT was neutropenia (16.0%). During CCRT, the investigational arm experienced statistically significantly more grade 3-4 toxicities (P < 0.001). CONCLUSION:NACT improved tumour control compared with CCRT alone in locoregionally advanced NPC, particularly at distant sites. However, there was no early gain in OS. Longer follow-up is needed to determine the eventual therapeutic efficacy.
Authors: Kenneth C W Wong; Edwin P Hui; Kwok-Wai Lo; Wai Kei Jacky Lam; David Johnson; Lili Li; Qian Tao; Kwan Chee Allen Chan; Ka-Fai To; Ann D King; Brigette B Y Ma; Anthony T C Chan Journal: Nat Rev Clin Oncol Date: 2021-06-30 Impact factor: 66.675