尼妥珠单抗联合PF方案诱导治疗局部晚期鼻咽癌的多中心临床研究
|
摘要
目的探讨尼妥珠单抗联合PF方案(顺铂+氟尿嘧啶)的诱导治疗在后续接受同期放化疗的局部晚期鼻咽癌患者中的安全性及作用。方法 118例Ⅲ～Ⅳa期鼻咽癌患者纳入研究,随机分为NPF组58例(尼妥珠单抗联合PF方案诱导治疗组)和TPF组60例(多西他赛、顺铂、氟尿嘧啶方案诱导化疗组),2周期诱导治疗后,所有患者均接受顺铂同期的调强放射治疗(IMRT),比较两组的安全性、近期疗效。结果与TPF组比较,NPF组诱导治疗对于颈部淋巴结有更显著的疗效(P=0.036);而诱导治疗的原发病灶疗效、诱导治疗的总体疗效和全程治疗结束的即刻疗效评价比较,差异均无统计学意义(P>0.05)。诱导治疗期间,中性粒细胞减少、胃肠道反应较TPF组均显著改善(P=0.028, P=0.049)。同期放化疗阶段,与TPF组比较,NPF组的胃肠道反应、口腔黏膜炎及放射性皮炎均显著改善(P=0.038, P=0.041, P=0.035)。结论对于后续接受顺铂同期IMRT治疗的局部晚期鼻咽癌,尼妥珠单抗联合PF方案的诱导治疗具有更好的淋巴结缓解率,且不良反应更轻微;患者在后续的同期放化疗中耐受性更好,但远期疗效需要进一步随访观察。
Objective To investigate the safety and efficacy of the induction therapy of nimotuzumab combined with PF regimen(cisplatin+5-fluorouracil) in the follow-up treatment of locally advanced nasopharyngeal carcinoma patients received concurrent chemoradiotherapy. Methods We included 118 patients with stage Ⅲ-Ⅳ a nasopharyngeal carcinoma, 58 cases in NPF group(induction therapy of nimotuzumab combined with PF regimen) and 60 cases in TPF group(induction chemotherapy of docetaxel,cisplatin and fluorouracil regimen). After two cycles of induction therapy, all patients received concurrent cisplatin and intensity-modulated radiotherapy(IMRT), and the safety and short-term efficacy of the two groups were compared. Results Compared with TPF group, NPF induction therapy was more effective for cervical lymph nodes(P=0.036); however, there was no significant difference in the effect of induction therapy on primary lesions, overall effect or the immediate effect of the whole course of treatment(P>0.05).Compared with TPF group, neutropenia and gastrointestinal reaction in the NPF group was significantly improved during the induction therapy(P=0.028, P=0.049); gastrointestinal reaction, oral mucositis and radiation dermatitis in the NPF group were significantly improved during the concurrent chemoradiotherapy(P=0.038, P=0.041, P=0.035). Conclusion For locally advanced nasopharyngeal carcinoma patients received cisplatin concurrent IMRT, the induction therapy of nimotuzumab combined with PF regimen have a better lymph node remission rate and mild adverse reactions. Patients had better tolerance in subsequent concurrent chemoradiotherapy, but the long-term efficacy requires further follow-up observation.
Objective To investigate the safety and efficacy of the induction therapy of nimotuzumab combined with PF regimen(cisplatin+5-fluorouracil) in the follow-up treatment of locally advanced nasopharyngeal carcinoma patients received concurrent chemoradiotherapy. Methods We included 118 patients with stage Ⅲ-Ⅳ a nasopharyngeal carcinoma, 58 cases in NPF group(induction therapy of nimotuzumab combined with PF regimen) and 60 cases in TPF group(induction chemotherapy of docetaxel,cisplatin and fluorouracil regimen). After two cycles of induction therapy, all patients received concurrent cisplatin and intensity-modulated radiotherapy(IMRT), and the safety and short-term efficacy of the two groups were compared. Results Compared with TPF group, NPF induction therapy was more effective for cervical lymph nodes(P=0.036); however, there was no significant difference in the effect of induction therapy on primary lesions, overall effect or the immediate effect of the whole course of treatment(P>0.05).Compared with TPF group, neutropenia and gastrointestinal reaction in the NPF group was significantly improved during the induction therapy(P=0.028, P=0.049); gastrointestinal reaction, oral mucositis and radiation dermatitis in the NPF group were significantly improved during the concurrent chemoradiotherapy(P=0.038, P=0.041, P=0.035). Conclusion For locally advanced nasopharyngeal carcinoma patients received cisplatin concurrent IMRT, the induction therapy of nimotuzumab combined with PF regimen have a better lymph node remission rate and mild adverse reactions. Patients had better tolerance in subsequent concurrent chemoradiotherapy, but the long-term efficacy requires further follow-up observation.
引文
[1]Lang J,Gao L,Guo Y,et al.Comprehensive treatment of squamous cell cancer of head and neck:hinese expert consensus2013[J].Future Oncol,2014,10(9):1635-48.
[2]Sun Y,Li WF,Chen NY,et al.Induction chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma:a phase 3,multicentre,randomised controlled trial[J].Lancet Oncol,2016,17(11):1509-20.
[3]Kong L,Zhang Y,Hu C,et al.Effects of Induction Docetaxel,Platinum,and Fluorouracil Chemotherapy in Patients With StageⅢorⅣA/B Nasopharyngeal Cancer Treated With Concurrent Chemoradiation Therapy:Final Results of 2 Parallel Phase 2Clinical Trials[J].Cancer,2017,123(12):2258-67.
[4]马雄辉,梁彩霞,江丹贤,等.TPF诱导化疗或PF诱导化疗联合同期放化疗治疗局部晚期鼻咽癌的临床观察[J].中国癌症杂志,2016,26(12):1018-24.[Ma XH,Liang CX,Jiang DX,et al.Clinical observation of TPF induction chemotherapy versus PF induction chemotherapy combined with concurrent chemoradiotherapy for the treatment of locoregionally advanced nasopharyngeal carcinoma[J].Zhongguo Ai Zheng Za Zhi,2016,26(12):1018-24.]
[5]杨佑琦,区晓敏,周鑫,等.GP、PF及TPF方案化疗联合调强适形放疗治疗鼻咽癌的临床疗效[J].中国癌症杂志,2018,28(8):602-8.[Yang YQ,Ou XM,Zhou X,et al.Clinical efficacy of GP,PF and TPF chemotherapy combined with intensity-modulated radiotherapy for nasopharyngeal carcinoma[J].Zhongguo Ai Zheng Za Zhi,2018,28(8):602-8.]
[6]Herbst RS,Shin DM.Monoclonal antibodies to target epidermal growth factor receptor-positive tumors:a new paradigm for cancer therapy[J].Cancer,2002,94(5):1593-611.
[7]Sun W,Long G,Wang J,et al.Prognostic role of epidermal growth factor receptor in nasopharyngeal carcinoma:a metaanalysis[J].Head Neck,2014,36(10):1508-16.
[8]Ma X,Huang J,Wu X,et al.Epidermal growth factor receptor could play a prognostic role to predict the outcome ofnasopharyngeal carcinoma:A meta-analysis[J].Cancer Biomark,2014,14(4):267-77.
[9]Peng H,Tang LL,Liu X,et al.Anti-epidermal growth factor receptor therapy concurrently withinduction chemotherapy in locoregionally advancednasopharyngeal carcinoma[J].Cancer Sci,2018,109(5):1609-16.
[10]黄晓东,易俊林,高黎,等.抗表皮生长因子受体单克隆抗体h-R3联合放疗治疗晚期鼻咽癌的Ⅱ期临床研究[J].中华肿瘤杂志,2007,29(3):197-201.[Huang XD,Yi JL,Gao L,et al.Multicenter phaseⅡclinical trial of humanized anti-epidermal factor receptor monoclonal antibody h-R3 combined with radiotherapy for locoregionally advanced nasopharyngeal carcinoma[J].Zhonghua Zhong Liu Za Zhi,2007,29(3):197-201.]
[11]Kong L,Lin Q,Lu JJ,et al.Radiation plus concurrent nimotuzumab versrs CDDP in locally advanced nasopharyngeal cancer:resuls of 3 randomised trial[C].2016,ASCO Abstract No:6002.
[12]Wang F,Jiang C,Ye Z,et al.Efficacy and safety of nimotuzumab with neoadjuvantchemotherapy followed by concurrent chemoradiotherapy forlocoregionally advanced nasopharyngeal carcinoma[J].Oncotarget,2017,8(43):75544-56.
[2]Sun Y,Li WF,Chen NY,et al.Induction chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma:a phase 3,multicentre,randomised controlled trial[J].Lancet Oncol,2016,17(11):1509-20.
[3]Kong L,Zhang Y,Hu C,et al.Effects of Induction Docetaxel,Platinum,and Fluorouracil Chemotherapy in Patients With StageⅢorⅣA/B Nasopharyngeal Cancer Treated With Concurrent Chemoradiation Therapy:Final Results of 2 Parallel Phase 2Clinical Trials[J].Cancer,2017,123(12):2258-67.
[4]马雄辉,梁彩霞,江丹贤,等.TPF诱导化疗或PF诱导化疗联合同期放化疗治疗局部晚期鼻咽癌的临床观察[J].中国癌症杂志,2016,26(12):1018-24.[Ma XH,Liang CX,Jiang DX,et al.Clinical observation of TPF induction chemotherapy versus PF induction chemotherapy combined with concurrent chemoradiotherapy for the treatment of locoregionally advanced nasopharyngeal carcinoma[J].Zhongguo Ai Zheng Za Zhi,2016,26(12):1018-24.]
[5]杨佑琦,区晓敏,周鑫,等.GP、PF及TPF方案化疗联合调强适形放疗治疗鼻咽癌的临床疗效[J].中国癌症杂志,2018,28(8):602-8.[Yang YQ,Ou XM,Zhou X,et al.Clinical efficacy of GP,PF and TPF chemotherapy combined with intensity-modulated radiotherapy for nasopharyngeal carcinoma[J].Zhongguo Ai Zheng Za Zhi,2018,28(8):602-8.]
[6]Herbst RS,Shin DM.Monoclonal antibodies to target epidermal growth factor receptor-positive tumors:a new paradigm for cancer therapy[J].Cancer,2002,94(5):1593-611.
[7]Sun W,Long G,Wang J,et al.Prognostic role of epidermal growth factor receptor in nasopharyngeal carcinoma:a metaanalysis[J].Head Neck,2014,36(10):1508-16.
[8]Ma X,Huang J,Wu X,et al.Epidermal growth factor receptor could play a prognostic role to predict the outcome ofnasopharyngeal carcinoma:A meta-analysis[J].Cancer Biomark,2014,14(4):267-77.
[9]Peng H,Tang LL,Liu X,et al.Anti-epidermal growth factor receptor therapy concurrently withinduction chemotherapy in locoregionally advancednasopharyngeal carcinoma[J].Cancer Sci,2018,109(5):1609-16.
[10]黄晓东,易俊林,高黎,等.抗表皮生长因子受体单克隆抗体h-R3联合放疗治疗晚期鼻咽癌的Ⅱ期临床研究[J].中华肿瘤杂志,2007,29(3):197-201.[Huang XD,Yi JL,Gao L,et al.Multicenter phaseⅡclinical trial of humanized anti-epidermal factor receptor monoclonal antibody h-R3 combined with radiotherapy for locoregionally advanced nasopharyngeal carcinoma[J].Zhonghua Zhong Liu Za Zhi,2007,29(3):197-201.]
[11]Kong L,Lin Q,Lu JJ,et al.Radiation plus concurrent nimotuzumab versrs CDDP in locally advanced nasopharyngeal cancer:resuls of 3 randomised trial[C].2016,ASCO Abstract No:6002.
[12]Wang F,Jiang C,Ye Z,et al.Efficacy and safety of nimotuzumab with neoadjuvantchemotherapy followed by concurrent chemoradiotherapy forlocoregionally advanced nasopharyngeal carcinoma[J].Oncotarget,2017,8(43):75544-56.