吉西他滨和顺铂诱导化疗治疗鼻咽癌。
Gemcitabine and Cisplatin Induction Chemotherapy in Nasopharyngeal Carcinoma.
机构信息
From the Departments of Radiation Oncology (Y.Z., L.C., Y.-P.C., W.-H.H., W.-F.L., L.-L.T., Y.-P.M., G.-Q.Z., R.S., X.L., R.G., F.H., J.-W.L., X.-J.D., C.X., N.L., Y.-Q.L., F.-Y.X., Ying Sun, J.M.), Medical Oncology (Y.-H.L.), and Nasopharyngeal Carcinoma (H.-Y.M.) and the Clinical Trials Center (Y.G.), Sun Yat-sen University Cancer Center, the State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy (Y.Z., L.C., Y.-P.C., W.-H.H., W.-F.L., L.-L.T., Y.-P.M., G.-Q.Z., R.S., X.L., R.G., F.H., J.-W.L., X.-J.D., C.X., N.L., Y.-Q.L., F.-Y.X., Ying Sun, J.M.), and the Department of Radiation Oncology, First Affiliated Hospital of Guangdong Pharmaceutical University (X.-C.W., Q.-F.S.), Guangzhou, the Cancer Center, Tongji Hospital Affiliated to Tongji Medical College (G.-Q.H., G.-X.L.), and the Cancer Center, Union Hospital, Tongji Medical College (K.-Y.Y., J.H.), Huazhong University of Science and Technology, Wuhan, the Department of Radiation Oncology, First People's Hospital of Foshan, Foshan (N.Z., S.-Q.L.), the Department of Radiation Oncology, Affiliated Cancer Hospital of Guangxi Medical University, Nanning (X.-D.Z., L.L.), the Department of Head and Neck Oncology, Affiliated Hospital of Guizhou Medical University, Guizhou Cancer Hospital, Guiyang (F.J., J.-H.L.), the Department of Radiation Oncology, XiJing Hospital of Fourth Military Medical University, Xi'an (M.S., J.Z.), the Cancer Center (Z.-B.C.), and the Department of Head and Neck Oncology (S.-Y.W., Q.-D.L.), Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, the Department of Radiation Oncology, Second Affiliated Hospital of Soochow University, Suzhou (Y.T., L.Z.), the Department of Radiation Oncology, Peking University Cancer Hospital, Beijing (Yan Sun, B.-M.Z.), and the Department of Radiation Oncology, Jiangxi Cancer Hospital, Nanchang (J.-G.L., Y.X.) - all in China; and the Divisions of Radiation Oncology and Medical Sciences, National Cancer Center Singapore, and the Oncology Academic Program, Duke-National University of Singapore Medical School - both in Singapore (M.L.K.C.).
出版信息
N Engl J Med. 2019 Sep 19;381(12):1124-1135. doi: 10.1056/NEJMoa1905287. Epub 2019 May 31.
BACKGROUND
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.
METHODS
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.
RESULTS
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.
CONCLUSIONS
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. (Funded by the Innovation Team Development Plan of the Ministry of Education and others; ClinicalTrials.gov number, NCT01872962.).
背景
铂类同步放化疗是局部晚期鼻咽癌患者的标准治疗方法。在 2 期临床试验中，吉西他滨联合顺铂诱导化疗显示出了有希望的疗效。
方法
在一项平行分组、多中心、随机、对照、3 期临床试验中，我们比较了吉西他滨联合顺铂作为诱导化疗联合同期放化疗与单纯同期放化疗的效果。局部晚期鼻咽癌患者以 1:1 的比例随机分配，接受吉西他滨（体表面积 1g/m2，第 1 和第 8 天）联合顺铂（第 1 天 80mg/m2），每 3 周为一个周期，共 3 个周期，联合放化疗（同期顺铂 100mg/m2，每 3 周为一个周期，联合强度调制放疗）或单纯放化疗。主要终点是意向治疗人群中的无复发生存率（即无疾病复发[远处转移或局部区域复发]或任何原因导致的死亡）。次要终点包括总生存、治疗依从性和安全性。
结果
共有 480 例患者入组（诱导化疗组 242 例，标准治疗组 238 例）。中位随访 42.7 个月后，诱导化疗组 3 年无复发生存率为 85.3%，标准治疗组为 76.5%（分层风险比为 0.51；95%置信区间为 0.34 至 0.77；P=0.001）。3 年总生存率分别为 94.6%和 90.3%（分层死亡风险比为 0.43；95%置信区间为 0.24 至 0.77）。共有 96.7%的患者完成了 3 个周期的诱导化疗。诱导化疗组 3 级或 4 级急性不良事件发生率为 75.7%，标准治疗组为 55.7%，诱导化疗组中性粒细胞减少症、血小板减少症、贫血、恶心和呕吐的发生率更高。诱导化疗组 3 级或 4 级迟发性毒性反应发生率为 9.2%，标准治疗组为 11.4%。
结论
与单纯放化疗相比，诱导化疗联合放化疗可显著提高局部晚期鼻咽癌患者的无复发生存率和总生存率。（由教育部创新团队发展计划等资助；ClinicalTrials.gov 编号，NCT01872962。）
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