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Induction chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: a phase 3, multicentre, randomised controlled trial

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单位: [1]Sun Yat Sen Univ, Dept Radiat Oncol, Ctr Canc, Collaborat Innovat Ctr Canc Med,State Key Lab Onc, 651 Dongfeng Rd East, Guangzhou 510060, Guangdong, Peoples R China; [2]Sichuan Univ, West China Hosp, Ctr Canc, Dept Radiat Oncol, Chengdu, Peoples R China; [3]First Peoples Hosp Foshan, Dept Radiat Oncol, Foshan, Peoples R China; [4]Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Oncol, Wuhan, Peoples R China; [5]Peking Univ, Sch Oncol, Dept Radiat Oncol, Beijing, Peoples R China; [6]Zhejiang Canc Hosp, Dept Radiat Oncol, Hangzhou, Zhejiang, Peoples R China; [7]Jiangxi Canc Hosp, Dept Radiat Oncol, Nanchang, Peoples R China; [8]Guangxi Med Univ, Canc Hosp, Dept Radiat Oncol, Nanning, Peoples R China; [9]Fudan Univ, Shanghai Med Coll, Dept Oncol, Dept Radiat Oncol,Shanghai Canc Ctr, Shanghai, Peoples R China; [10]Harbin Med Univ, Canc Hosp, Dept Radiat Oncol, Harbin, Peoples R China; [11]Sun Yat Sen Univ, Dept Nasopharyngeal Carcinoma, Collaborat Innovat Ctr Canc Med, Ctr Canc,State Key Lab Oncol South China, Guangzhou, Guangdong, Peoples R China; [12]Sun Yat Sen Univ, Clin Trials Ctr, Collaborat Innovat Ctr Canc Med, Ctr Canc,State Key Lab Oncol South China, Guangzhou, Guangdong, Peoples R China; [13]Sun Yat Sen Univ, Sch Publ Hlth, Dept Med Stat & Epidemiol, Guangzhou, Guangdong, Peoples R China
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Background The value of adding cisplatin, fluorouracil, and docetaxel (TPF) induction chemotherapy to concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma is unclear. We aimed to compare TPF induction chemotherapy plus concurrent chemoradiotherapy with concurrent chemoradiotherapy alone in a suitably powered trial. Methods We did an open-label, phase 3, multicentre, randomised controlled trial at ten institutions in China. Patients with previously untreated, stage III-IVB (except T3-4N0) nasopharyngeal carcinoma, aged 18-59 years without severe comorbidities were enrolled. Eligible patients were randomly assigned (1: 1) to receive induction chemotherapy plus concurrent chemoradiotherapy or concurrent chemoradiotherapy alone (three cycles of 100 mg/m(2) cisplatin every 3 weeks, concurrently with intensity-modulated radiotherapy). Induction chemotherapy was three cycles of intravenous docetaxel (60 mg/m(2) on day 1), intravenous cisplatin (60 mg/m(2) on day 1), and continuous intravenous fluorouracil (600 mg/m(2) per day from day 1 to day 5) every 3 weeks before concurrent chemoradiotherapy. Randomisation was by a computer-generated random number code with a block size of four, stratified by treatment centre and disease stage (III or IV). Treatment allocation was not masked. The primary endpoint was failure-free survival calculated from randomisation to locoregional failure, distant failure, or death from any cause; required sample size was 476 patients (238 per group). We did efficacy analyses in our intention-to-treat population. The follow-up is ongoing; in this report, we present the 3-year survival results and acute toxic effects. This trial is registered with ClinicalTrials.gov, number NCT01245959. Findings Between March 1, 2011, and Aug 22, 2013, 241 patients were assigned to induction chemotherapy plus concurrent chemoradiotherapy and 239 to concurrent chemoradiotherapy alone. After a median follow-up of 45 months (IQR 38-49), 3-year failure-free survival was 80% (95% CI 75-85) in the induction chemotherapy plus concurrent chemoradiotherapy group and 72% (66-78) in the concurrent chemoradiotherapy alone group (hazard ratio 0.68, 95% CI 0.48-0.97; p=0.034). The most common grade 3 or 4 adverse events during treatment in the 239 patients in the induction chemotherapy plus concurrent chemoradiotherapy group versus the 238 patients in concurrent chemoradiotherapy alone group were neutropenia (101 [42%] vs 17 [7%]), leucopenia (98 [41%] vs 41 [17%]), and stomatitis (98 [41%] vs 84 [35%]). Interpretation Addition of TPF induction chemotherapy to concurrent chemoradiotherapy significantly improved failure-free survival in locoregionally advanced nasopharyngeal carcinoma with acceptable toxicity. Long-term follow-up is required to determine long-term efficacy and toxicities.

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基金编号: 2007037 2014BAI09B10 201400000001 2013B020400004 2016YFC0902000

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出版当年[2015]版:
大类 | 1 区 医学
小类 | 1 区 肿瘤学
最新[2025]版:
大类 | 1 区 医学
小类 | 1 区 肿瘤学
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出版当年[2014]版:
Q1 ONCOLOGY
最新[2023]版:
Q1 ONCOLOGY

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第一作者单位: [1]Sun Yat Sen Univ, Dept Radiat Oncol, Ctr Canc, Collaborat Innovat Ctr Canc Med,State Key Lab Onc, 651 Dongfeng Rd East, Guangzhou 510060, Guangdong, Peoples R China;
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通讯机构: [1]Sun Yat Sen Univ, Dept Radiat Oncol, Ctr Canc, Collaborat Innovat Ctr Canc Med,State Key Lab Onc, 651 Dongfeng Rd East, Guangzhou 510060, Guangdong, Peoples R China;
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