您的位置:山东大学 -> 科技期刊社 -> 《山东大学学报(医学版)》

山东大学学报 (医学版) ›› 2022, Vol. 60 ›› Issue (7): 110-117.doi: 10.6040/j.issn.1671-7554.0.2021.1306

• 临床医学 • 上一篇    下一篇

DC-CIK细胞联合EGFR-TKI治疗35例老年晚期EGFR突变肺癌的效果

王福立1,孙银萍1,秦杰2,荣建胜3   

  1. 1.淄博市中心医院肿瘤科, 山东 淄博 255000;2.高青县人民医院肿瘤科, 山东 高青 256300;3.淄博市中心医院病理科, 山东 淄博 255000
  • 发布日期:2022-07-27
  • 通讯作者: 孙银萍. E-mail:836240762@qq.com
  • 基金资助:
    山东省医药卫生科技发展计划项目(2017WS561);山东省淄博市科学技术发展计划项目(2017kj010004)

Efficacy of DC-CIK cells combined with EGFR-TKI for 35 elderly patients with advanced EGFR-mutant lung cancer

WANG Fuli1, SUN Yinping1, QIN Jie2, RONG Jiansheng3   

  1. 1. Department of Oncology, Zibo Central Hospital, Zibo 255000, Shandong, China;
    2. Department of Oncology, Gaoqing Peoples Hospital, Gaoqing 256300, Shandong, China;
    3. Department of Pathology, Zibo Central Hospital, Zibo 255000, Shandong, China
  • Published:2022-07-27

摘要: 目的 探讨树突状细胞-细胞因子诱导的杀伤细胞(DC-CIK)联合表皮生长因子受体酪氨酸激酶抑制剂(EGRF-TKI)治疗老年晚期表皮生长因子受体(EGFR)突变肺癌的临床疗效。 方法 将70例Ⅳ期EGFR突变肺癌患者分为治疗组和对照组。治疗组35例,给予DC-CIK细胞治疗联合吉非替尼或厄洛替尼靶向治疗;对照组35例,给予吉非替尼或厄洛替尼靶向治疗。 结果 治疗组的疾病控制率(DCR)为88.6%,高于对照组的68.6%(P=0.041),治疗组生活质量评分改善率为71.4%,高于对照组的45.7%(P=0.029),差异均有统计学意义。治疗组和对照组的1年、2年和3年总生存(OS)率分别为62.9% vs 57.1%、37.1% vs 31.4%和8.6% vs 2.9%,两组比较差异无统计学意义(P=0.217)。治疗组和对照组的1年、2年和3年无进展生存(PFS)率分别为57.1% vs 31.4%、20.0% vs 5.7%和2.9% vs 0%,两组差异有统计学意义(P=0.005)。多因素分析显示,腺癌(HR=0.178,95%CI:0.061~0.523)及高分化(HR=0.058,95%CI:0.015~0.228)患者OS更长,腺癌(HR=0.271,95%CI:0.094~0.777)及高分化(HR=0.089,95%CI:0.029~0.272)患者PFS也更长。治疗组和对照组不良反应发生率差异无统计学意义(P>0.05)。 结论 DC-CIK细胞联合EGRF-TKI可以提高晚期老年EGFR突变肺癌患者的疾病控制率和生活质量,延长患者的PFS。

关键词: 肺癌, 靶向治疗, 树突状细胞, 细胞因子诱导的杀伤细胞, 吉非替尼, 厄洛替尼

Abstract: Objective To investigate the clinical efficacy of dendritic cells-cytokine-induced killer cells(DC-CIK cells)combined with epidermal growth factor receptor-tyrosine kinase inhibitor(EGRF-TKI)for elderly patients with advanced EGFR-mutant lung cancer. Methods A total of 70 patients with stage IV lung cancer were divided into treatment group and control group. In the treatment group, 35 patients received DC-CIK cell therapy combined with gefitinib or erlotinib targeted therapy. In the control group, 35 patients received gefitinib or erlotinib targeted therapy. Results The disease control rate(DCR)of the treatment group and control group were 88.6% and 68.6%, respectively, with significant difference(P=0.041). The improvement rate of patients quality of life was significantly higher in the treatment group than in the control group(71.4% vs 45.7%, P=0.029). The 1-year, 2-year, and 3-year overall survival(OS)rates of the treatment group and control group were 62.9% vs 57.1%, 37.1% vs 31.4%, and 8.6% vs 2.9%, respectively, with no significant differences(P=0.217). The 1-year, 2-year, and 3-year progression-free survival(PFS)rates of the treatment group and control group were 57.1% vs 31.4%, 20.0% vs 5.7%, and 2.9% vs 0, respectively, with significant differences(P=0.005). Multivariate analysis showed that patients with adenocarcinoma(HR=0.178, 95%CI: 0.061-0.523)and well-differentiated cancer(HR=0.058, 95%CI: 0.015-0.228)had longer OS, and patients with adenocarcinoma(HR=0.271, 95%CI: 0.094-0.777)and well-differentiated cancer(HR=0.089, 95%CI: 0.029-0.272)also had longer PFS. There was no statistically significant difference in the incidence of adverse reactions between the two groups(P>0.05). Conclusion DC-CIK cells combined with EGRF-TKI can improve the disease control rate and patients quality of life, and prolong the PFS in elderly patients with advanced EGFR-mutant lung cancer.

Key words: Lung cancer, Targeted therapy, Dendritic cells, Cytokine-induced killer cells, Gefitinib, Erlotinib

中图分类号: 

  • R734
[1] Patel SA, Weiss J. Advances in the treatment of non-small cell lung cancer: immunotherapy[J]. Clin Chest Med, 2020, 41(2): 237-247.
[2] Wu F, Wang L, Zhou C. Lung cancer in China: current and prospect[J]. Curr Opin Oncol, 2021, 33(1): 40-46.
[3] Leighl NB, Karaseva N, Nakagawa K, et al. Patient-reported outcomes from FLAURA: osimertinib versus erlotinib or gefitinib in patients with EGFR-mutated advanced non-small-cell lung cancer[J]. Eur J Cancer, 2020, 125: 49-57. doi: 10.1016/j.ejca.2019.11.006.
[4] 王建丽,王筱静,孙玉莲,等.吉非替尼联合化疗治疗50例晚期非小细胞肺癌患者的疗效[J].山东大学学报(医学版),2019, 57(11): 20-26. WANG Jianli, WANG Xiaojing, SUN Yulian, et al. Clinical effect of gefitinib combined with chemotherapy on patients with advanced non-small cell lung cancer[J]. Journal of Shandong University(Health Sciences), 2019, 57(11): 20-26.
[5] Liu YF, Liu HB, Liu HS, et al. Dendritic cell-activated cytokine-induced killer cell-mediated immunotherapy is safe and effective for cancer patients >65 years old[J]. Oncol Lett, 2016, 12(6): 5205-5210.
[6] Wylie B, Macri C, Mintern JD, et al. Dendritic cells and cancer: from biology to therapeutic intervention [J]. Cancers(Basel), 2019, 11(4): 521.
[7] Gardner A, de Mingo Pulido A, Ruffell B. Dendritic cells and their role in immunotherapy[J]. Front Immunol, 2020, 11: 924. doi: 10.3389/fimmu.2020.00924.
[8] Cao J, Kong FH, Liu X, et al. Immunotherapy with dendritic cells and cytokine-induced killer cells for hepatocellular carcinoma: a meta-analysis[J]. World J Gastroenterol, 2019, 25(27): 3649-3663.
[9] Hung LVM, Ngo HT, Van Pham P. Clinical trials with cytokine-induced killer cells and CAR-T cell transplantation for non-small cell lung cancer treatment[J]. Adv Exp Med Biol, 2020, 1292:113-130. doi: 10.1007/5584_2020_522.
[10] Kim JH, Min SJ, Jang HJ, et al. Comparison of RECIST 1.0 and RECIST 1.1 in patients with metastatic cancer: a pooled analysis[J]. J Cancer, 2015, 6(4): 387-393.
[11] 谭诗生,李杭,罗健,等.欧洲癌症研究与治疗组织研制的生活质量核心调查问卷第3版中文版:生活质量调查问卷测评[J].中国临床康复,2006,10(4):23-27. TAN Shisheng, LI Hang, LUO Jian, et al. Assessment on the standard Chinese version of quality of life core questionnaire version 3.0 designed by European Organization for Reasearch and Treatment of Cancer[J]. Chinese Journal of Clinical Rehabilitation, 2006, 10(4): 23-27.
[12] Mok TS, Wu YL, Thongprasert S, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma[J]. N Engl J Med, 2009, 361(10): 947-957.
[13] Zhou C, Wu YL, Chen G, et al. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer(OPTIMAL, CTONC-0802): a multicentre, open-label, randomised, phase 3 study[J]. Lancet Oncol, 2011, 12(8): 735-742.
[14] Takahashi K, Saito H, Hasegawa Y, et al. First-line gefitinib therapy for elderly patients with non-small cell lung cancer harboring EGFR mutation: Central Japan Lung Study Group 0901[J]. Cancer Chemother Pharmaco, 2014, l74(4): 721-727.
[15] Inoue Y, Inui N, Asada K, et al. Phase II study of erlotinib in elderly patients with non-small cell lung cancer harboring epidermal growth factor receptor mutations[J]. Cancer Chemother Pharmacol, 2015, 76(1): 155-161.
[16] Kashiwabara K, Fujii S, Tsumura S, et al. Overall survival of super-elderly(85 years or older)advanced non-small cell lung cancer patients with active epidermal growth factor receptor mutations receiving first-line gefitinib therapy: a single-institute retrospective study[J]. J Cancer Res Clin Oncol, 2021, 147(1): 287-293.
[17] Hirsch FR, Sequist LV, Gore I, et al. Long-term safety and survival with gefitinib in select patients with advanced non-small cell lung cancer: results from the US IRESSA clinical access program(ICAP)[J]. Cancer, 2018, 124(11): 2407-2414.
[18] Roberto RC, Walter PD. Targeted therapy and checkpoint immunotherapy in lung cancer[J]. Surg Pathol Clin, 2020, 13(1): 17-33.
[19] 于金明,颜薇薇,陈大卫.肺癌放射免疫新实践[J].山东大学学报(医学版),2021,59(9):1-8. YU Jinming, YAN Weiwei, CHEN Dawei. New practice of radio-immunotherapy for lung cancer[J]. Journal of Shandong University(Health Sciences), 2021, 59(9): 1-8.
[20] Scheper W, Kelderman S, Fanchi LF, et al. Low and variable tumor reactivity of the intratumoral TCR repertoire in human cancers[J]. Nat Med, 2019, 25(1): 89-94.
[21] Wang S, Wang X, Zhou X, et al. DC-CIK as a widely applicable cancer immunotherapy [J]. Expert Opin Biol Ther, 2020, 20(6): 601-607.
[22] Zhao Y, Qiao G, Wang X, et al. Combination of DC/CIK adoptive T cell immunotherapy with chemotherapy in advanced non-small-cell lung cancer(NSCLC)patients: a prospective patients preference-based study(PPPS)[J]. Clin Transl Oncol, 2019, 21(6): 721-728.
[23] Solmaz S, Nazila A, Behzad M, et al. Promising immunotherapy: highlighting cytokine-induced killer cells[J]. J Cell Biochem, 2019, 120(6): 8863-8883.
[24] Wang L, Dai Y, Zhu F, et al. Efficacy of DC-CIK-based immunotherapy combined with chemotherapy in the treatment of intermediate to advanced non-small cell lung cancer[J]. Am J Transl Res, 2021, 13(11): 13076-13083.
[25] Song HP, Liu SJ, Zhao ZY, et al. Increased cycles of DC/CIK immunotherapy decreases frequency of Tregs in patients with resected NSCLC[J]. Int Immunopharmacol, 2017, 52: 197-202. doi: 10.1016/j.intimp.2017.09.014.
[26] Xiao Z, Wang CQ, Zhou MH, et al. The antitumor immunity and tumor responses of chemotherapy with or without DC-CIK for non-small-cell lung cancer in China: a meta-analysis of 28 randomized controlled trials[J]. J Immunol Res, 2018,13:1-18. doi: 10.1155/2018/9081938.
[27] Zhu XP, Xu YH, Zhou J, et al. A clinical study evaluating dendritic and cytokine-induced killer cells combined with concurrent radiochemotherapy for stage IIIB non-small cell lung cancer[J]. Genet Mol Res, 2015, 14(3): 10228-10235.
[1] 韩靖,贾春玲. 肺癌患者胸外手术前治疗牙周基础疾病对预防术后肺炎发生的效果评价[J]. 山东大学学报 (医学版), 2022, 60(9): 113-118.
[2] 高中霞,张铭,樊明德,谭晨阳,王梦迪,王超,樊跃飞,丁守銮,王成伟. 伽玛刀治疗81例肺癌脑转移瘤的疗效及预后因素[J]. 山东大学学报 (医学版), 2022, 60(8): 44-49.
[3] 相宇娇,刘强,刘璐,石艳. 原发免疫性血小板减少症树突状细胞异常免疫反应机制[J]. 山东大学学报 (医学版), 2022, 60(7): 89-97.
[4] 秦静,杨飞,陈谦,夏涵岱,刘延国,王秀问. 晚期驱动基因阴性、PD-L1表达阴性非鳞非小细胞肺癌一线治疗方案的网状Meta分析[J]. 山东大学学报 (医学版), 2022, 60(7): 74-82.
[5] 陈兆波,方敏,薛浩然,刘春艳. 去泛素化酶USP35促进非小细胞肺癌细胞迁移和侵袭[J]. 山东大学学报 (医学版), 2022, 60(4): 30-37.
[6] 高会江,魏煜程. 微创袖式肺叶切除手术:免疫治疗时代的机遇和挑战[J]. 山东大学学报 (医学版), 2022, 60(11): 23-27.
[7] 彭岳,刘雷,李原,别凤龙,周博伦,李润泽,冀瑛,白广宇,谭锋维,高禹舜,牟巨伟,薛奇,邱斌,高树庚. 解剖性部分肺叶切除术及围术期加速康复外科的临床综合应用[J]. 山东大学学报 (医学版), 2022, 60(11): 44-53.
[8] 高树庚. 加速康复外科在肺癌围术期管理中的应用[J]. 山东大学学报 (医学版), 2022, 60(11): 1-10.
[9] 韩丁培,严越,曹羽钦,孙昕,胡琰霞,汪敏娴,罗艳,施咏梅,谢青,杭钧彪,李鹤成. 加速康复外科理念在胸外科临床实践指导的瑞金医院专家共识[J]. 山东大学学报 (医学版), 2022, 60(11): 11-16.
[10] 刘会宁,彭军,任迎春,杨光,王文豪,刘金锋,田勍. 34例胸腔镜下肺楔形切除与21例肺段切除对位于肺段P区的ⅠA1期非小细胞肺癌治疗比较[J]. 山东大学学报 (医学版), 2022, 60(11): 38-43.
[11] 丁子琛,王浩桦,周立雯,丛慧文,李承圣,包绮晗,杨毅,王廉源,王素珍,石福艳. 基于贝叶斯累加回归树模型的非小细胞肺癌患者个性化疗效研究[J]. 山东大学学报 (医学版), 2022, 60(10): 92-98.
[12] 哈春芳,李茹月. 卵巢癌耐药机制与靶向治疗策略的研究进展[J]. 山东大学学报 (医学版), 2021, 59(9): 117-123.
[13] 于金明,颜薇薇,陈大卫. 肺癌放射免疫新实践[J]. 山东大学学报 (医学版), 2021, 59(9): 1-8.
[14] 焉传祝,王伟,纪坤乾,赵玉英. 线粒体与脑疾病[J]. 山东大学学报 (医学版), 2020, 1(8): 34-41.
[15] 陈安静,张训. 靶向小类泛素化修饰的胶质瘤治疗新策略[J]. 山东大学学报 (医学版), 2020, 1(8): 88-94.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
[1] 索东阳,申飞,郭皓,刘力畅,杨惠敏,杨向东. Tim-3在药物性急性肾损伤动物模型中的表达及作用机制[J]. 山东大学学报 (医学版), 2020, 1(7): 1 -6 .
[2] 马青源,蒲沛东,韩飞,王超,朱洲均,王维山,史晨辉. miR-27b-3p调控SMAD1对骨肉瘤细胞增殖、迁移和侵袭作用的影响[J]. 山东大学学报 (医学版), 2020, 1(7): 32 -37 .
[3] 龙婷婷,谢明,周璐,朱俊德. Noggin蛋白对小鼠脑缺血再灌注损伤后学习和记忆能力与齿状回结构的影响[J]. 山东大学学报 (医学版), 2020, 1(7): 15 -23 .
[4] 李宁,李娟,谢艳,李培龙,王允山,杜鲁涛,王传新. 长链非编码RNA AL109955.1在80例结直肠癌组织中的表达及对细胞增殖与迁移侵袭的影响[J]. 山东大学学报 (医学版), 2020, 1(7): 38 -46 .
[5] 张宝文,雷香丽,李瑾娜,罗湘俊,邹容. miR-21-5p靶向调控TIMP3抑制2型糖尿病肾病小鼠肾脏系膜细胞增殖及细胞外基质堆积[J]. 山东大学学报 (医学版), 2020, 1(7): 7 -14 .
[6] 付洁琦,张曼,张晓璐,李卉,陈红. Toll样受体4抑制过氧化物酶体增殖物激活受体γ加重血脂蓄积的分子机制[J]. 山东大学学报 (医学版), 2020, 1(7): 24 -31 .
[7] 徐玉香,刘煜东,张蓬,段瑞生. 101例脑小血管病患者脑微出血危险因素的回顾性分析[J]. 山东大学学报 (医学版), 2020, 1(7): 67 -71 .
[8] 丁祥云,于清梅,张文芳,庄园,郝晶. 胰岛素样生长因子II在84例多囊卵巢综合征患者颗粒细胞中的表达和促排卵结局的相关性[J]. 山东大学学报 (医学版), 2020, 1(7): 60 -66 .
[9] 史爽,李娟,米琦,王允山,杜鲁涛,王传新. 胃癌miRNAs预后风险评分模型的构建与应用[J]. 山东大学学报 (医学版), 2020, 1(7): 47 -52 .
[10] 肖娟,肖强,丛伟,李婷,丁守銮,张媛,邵纯纯,吴梅,刘佳宁,贾红英. 两种甲状腺超声数据报告系统诊断效能的比较[J]. 山东大学学报 (医学版), 2020, 1(7): 53 -59 .