Clinical efficacy of erlotinib combined with concurrent whole brain radiotherapy in treatment of multiple brain metastases from EGFR-mutant lung adenocarcinoma
Sun Di, Zhang Sheng, Lin Guangyong, Zhang Youting
Department of Pharmacy,Second Affiliated Hospital of Wenzhou Medical University,Wenzhou 325000,China (Sun D,Lin GY,Zhang YT); Department of General Surgery,General Surgery of Workers' Hospital in Ningxia Hui Nationality Autonomous Region,Yinchuan 750000,China (Zhang S)
Abstract:Objective To investigate the clinical efficacy and safety of erlotinib combined with concurrent whole brain radiotherapy (WBRT) in the treatment of multiple brain metastases from lung adenocarcinoma, and to provide Objective evidence for improving the prognosis of patients. Methods Eighty-nine patients with brain metastases from epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma who were admitted to our hospital were divided into experimental group (n=45) and control group (n=44) according to the different treatment methods. The experimental group received erlotinib combined with concurrent WBRT. The control group received oral administration of erlotinib alone for 28 d and then received concurrent WBRT. The survival rates were calculated using the Kaplan-Meier method and analyzed using the log-rank test. The other data were analyzed by the chi-square test. Results The Objective response rate was significantly higher in the experimental group than in the control group (78% vs. 55%, P=0.000). The median progression-free survival (PFS) time in the experimental group and the control group were 9.1 months (95% confidence interval[CI]:5.18-12.47) and 5.6 months (95%CI:3.46-9.12), respectively (P=0.078). The median overall survival (OS) time in the experimental group and the control group were 14.3 months (95%CI:9.51-17.82) and 9.7 months (95%CI:4.59-16.74), respectively (P=0.032). The incidence rates of headache and dizziness were significantly higher in the experimental group than in the control group (38% vs. 14%, P=0.029;33% vs. 9%, P=0.020). Conclusions In the treatment of multiple brain metastases from EGFR-mutant lung adenocarcinoma, erlotinib combined with concurrent WBRT is superior to erlotinib alone. The combination therapy increases PFS and OS time of the nervous system in patients.
Sun Di,Zhang Sheng,Lin Guangyong et al. Clinical efficacy of erlotinib combined with concurrent whole brain radiotherapy in treatment of multiple brain metastases from EGFR-mutant lung adenocarcinoma[J]. Chinese Journal of Radiation Oncology, 2018, 27(5): 463-466.
[1]蔡忠福,欧阳学农,余宗阳.非小细胞肺癌脑转移药物治疗的研究进展[J].临床肿瘤学杂志,2014,19(4):379-382. Cai ZF,Ouyang XN,Yu ZY.Progress of drugs in non-small cell lung cancer with brain metastasis[J].Chin Clin Oncol,2014,19(4):379-382. [2]Mujoomdar A,Austin JHM,Malhotra R,et al. Clinical predictors of metastatic disease to the brain from non-small-cell lung carcinoma:primary tumor size,cell type,and lymph node metastases[J].Radiology,2007,242(3):882-888.DOI:10.1148/radiol.2423051707. [3]殷蔚伯,余子豪,徐国镇,等.肿瘤放射治疗学[M].4版.北京:中国协和医科大学出版社,2008:1200-1206. Yin WB,Yu ZH,Xu GZ,et al. Radiation oncology[M].4th ed. Beijing:Peking Union Medical College Press,2008:1200-1206. [4]朱虹,李云海,王洪林,等.非小细胞肺癌脑转移厄洛替尼结合WBRT治疗的理论基础和研究进展[J].国际肿瘤学杂志,2014,41(6):435-438.DOI:10.3760/cma.j.issn.1673-422X.2014.06.011. Zhu H,Li YH,Wang HL,et al. The theoretical foundation and research progress for erlotinib combined with whole brain radiotherapy for the treatment for non-small cell lung cancer patients with brain metastases[J].J Int Oncol,2014,41(6):435-438.DOI:10.3760/cma.j.issn.1673-422X.2014.06.011. [5]顾红芳,许春明,王向前,等.厄洛替尼联合WBRT治疗肺腺癌伴脑转移的临床观察[J].临床肿瘤学杂志,2014,19(12):1118-1122. Gu HF,Xu CM,Wang XQ,et al. Clinical observation of erlotinib combined with whole brain radiotherapy for lung adenocarcinoma with brain metastases[J].Chin Clin Oncol,2014,19(12):1118-1122. [6]Antoni D,Noël G.Radiotherapy of brain metastases according to the GPA score (Graded Prognostic Assessment)[J].Cancer Radiother,2013,17(5-6):424-427.DOI:10.1016/j.canrad.2013.06.030. [7]Zhang Q,Chen J,Yu XL,et al. Systemic treatment after whole-brain radiotherapy may improve survival in RPA class Ⅱ/Ⅲ breast cancer patients with brain metastasis[J].J Neuro-Oncol,2013,114(2):181-189.DOI:10.1007/s11060-013-1169-4. [8]Kong W,Jarvis CR,Sutton DS,et al. The use of palliative whole brain radiotherapy in the management of brain metastases[J].Clin Oncol,2012,24(10):149-158.DOI:10.1016/j.clon.2012.08.004. [9]Zimmermann S,Dziadziuszko R,Peters S.Indications and limitations of chemotherapy and targeted agents in non-small cell lung cancer brain metastases[J].Cancer Treat Rev,2014,40(6):716-722.DOI:10.1016/j.ctrv.2014.03.005. [10]Welsh JW,Komaki R,Amini A,et al. Phase Ⅱ trial of erlotinib plus concurrent whole-brain radiation therapy for patients with brain metastases from non-small-cell lung cancer[J].J Clin Oncol,2013,31(7):895-902.DOI:10.1200/JCO.2011.40.1174. [11]庄洪卿,袁智勇,王军,等.WBRT联合厄洛替尼治疗肺腺癌多发脑转移的理论基础和研究进展[J].中华放射肿瘤学杂志,2012,21(6):546-549.DOI:10.3760/cma.j.issn.1004-4221.2012.06.019. Zhuang HQ,Yuan ZY,Wang J,et al. The theoretical basis and research progress on the treatment of multiple brain metastases from lung adenocarcinoma with total brain radiotherapy combined with felodipine[J].Chin J Radiat Oncol,2012,21(6):546-549.DOI:10.3760/cma.j.issn.1004-4221.2012.06.019. [12]Morris PG,Correa DD,Yahalom J,et al. Rituximab,methotrexate,procarbazine,and vincristine followed by consolidation reduced-dose whole-brain radiotherapy and cytarabine in newly diagnosed primary CNS lymphoma:final results and long-term outcome[J].J Clin Oncol,2013,31(31):3971-3979.DOI:10.1200/JCO.2013.50.4910. [13]Zhuang H,Yuan Z,Wang J,et al. Phase Ⅱ study of whole brain radiotherapy with or without erlotinib in patients with multiple brain metastases from lung adenocarcinoma[J].Drug Des Devel Ther,2013,7:1179-1186.DOI:10.2147/DDDT.S53011. [14]Hata A,Kaji R,Fujita S,et al. High-dose erlotinib for refractory brain metastases in a patient with relapsed non-small cell lung cancer[J].J Thorac Oncol,2011,6(3):653-654. [15]万欣,王军,吴凤鹏,等.厄洛替尼治疗晚期非小细胞肺癌临床观察[J].中华肿瘤防治杂志,2014,21(19):1538-1543.DOI:10.16073/j.cnki.cjcpt.2014.19.014. Wan X,Wang J,Wu FP,et al. Efficacy in stage Ⅳ non-small cell lung cancer patients treated with Erlotinib[J].Chin J Cancer Prev Treat,2014,21(19):1538-1543.DOI:10.16073/j.cnki.cjcpt.2014.19.014. [16]王小磊,刘德泽,石岩.厄洛替尼联合WBRT治疗非小细胞肺癌脑转移的研究进展[J].中国癌症防治杂志,2015,7(3):232-234.DOI:10.3969/j.issn.1674-5671.2015.03.22. Wang XL,Liu DZ,Shi Y.Advances in the treatment of brain metastasis of non-small cell lung cancer by combined with total brain radiotherapy[J].Chin J Cancer Prevent Control,2015,7(3):232-234.DOI:10.3969/j.issn.1674-5671.2015.03.22. [17]Deng YM,Feng WN,Wu J,et al. The concentration of erlotinib in the cerebrospinal fluid of patients with brain metastasis from non-small-cell lung cancer[J].Mol Clin Oncol,2014,2(1):116-120.DOI:10.3892/mco.2013.190. [18]王小磊,刘德泽,王民,等.厄洛替尼联合WBRT治疗非小细胞肺癌脑转移的临床观察[J].国际肿瘤学杂志,2015,42(11):809-812.DOI:10.3760/cma.j.issn.1673-422X.2015.11.003. Wang XL,Liu DZ,Wang M,et al. Clinical observation of erlotinib combined with whole brain radiation therapy for non-small cell lung cancer patients with brain metastases[J].J Int Oncol,2015,42(11):809-812.DOI:10.3760/cma.j.issn.1673-422X.2015.11.003. [19]Zhou L,Liu J,Xue JX,et al. Whole brain radiotherapy plus simultaneous in-field boost with image guided intensity-modulated radiotherapy for brain metastases of non-small cell lung cancer[J].Radiat Oncol,2014,9:117.DOI:10.1186/1748-717X-9-117.