A Randomized Controlled Trial Comparing Two Different Schedules for Cisplatin Treatment in Patients with Locoregionally Advanced Nasopharyngeal Cancer
Wei‐Xiong Xia, Xing Lv, Hu L, Guoying Liu, Rui Sun, Qi Zeng, Siwei Li, Hao‐Yuan Mo, Fei Han, Dong–Hua Luo, Qing Liu, Meng-Yun Shi, Yan‐Fang Ye, Jing Yang, Liang‐Ru Ke, Meng‐Yun Qiang, Wen‐Ze Qiu, Ya‐Hui Yu, Kui‐Yuan Liu, Xin-Jun Huang, Wang‐Zhong Li, Shu‐Hui Lv, Zhuo‐Chen Cai, Jingjing Miao, Ling Guo, Ming‐Yuan Chen, Ka–Jia Cao, Lin Wang, Chong Zhao, Pei‐Yu Huang, Qiuyan Chen, Yi‐Jun Hua, Lin‐Quan Tang, Chao‐Nan Qian, Hai‐Qiang Mai, Xiang Guo, Yan‐Qun Xiang
Abstract
Abstract Purpose: Previous studies suggest that a cumulative cisplatin dose of 200 mg/m2 might be adequate in the intensity-modulated radiation therapy (IMRT) era for locoregionally advanced nasopharyngeal carcinoma (LANPC). However, two cycles of once-every-3-weeks cisplatin at 100 mg/m2 has never been prospectively compared with standard once-a-week cisplatin regimen. Patients and Methods: This trial was conducted at three hospitals from 2011 to 2016. Patients who met the eligibility criteria were recruited (ChiCTR-TRC-12001979) and randomly assigned (1:1) via a computer-generated sequence to receive once-every-3-weeks cisplatin at 100 mg/m2 for two cycles or once-a-week cisplatin at 40 mg/m2 for six cycles concurrently with IMRT. Primary endpoint was failure-free survival and between-group absolute difference of 10% as the noninferiority margin. Results: A total of 510 patients were enrolled. Median follow-up time was 58.3 months with 85.4% of 3-year failure-free survival in the once-every-3-weeks group and 85.6% in the once-a-week group. An absolute difference of −0.2% (95% confidence interval, −6.3 to 5.9; Pnoninferiority = 0.0016). Acute toxicities of grade 3 or higher occurred in 55.8% in the once-every-3-weeks group and 66.3% in the once-a-week group (P = 0.015). The most common acute toxicities were hematologic abnormalities, including leukopenia (16% vs. 27%; P = 0.0022) and thrombocytopenia (1% vs. 5%; P = 0.015). The late grade 3–4 auditory loss rate was significantly lower in the once-every-3-weeks group than the once-a-week group (6% vs. 13%; P = 0.0039). Conclusions: Once-every-3-weeks cisplatin as concurrent chemoradiotherapy is noninferior to once-a-week cisplatin in the treatment efficacy in the LANPC. Although both regimens are well tolerated, severe acute toxicities and late-onset auditory loss are higher in the once-a-week group.