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

doi:10.6040/j.issn.1671-7554.0.2021.1306

摘要/Abstract

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

王福立,孙银萍,秦杰,荣建胜. DC-CIK细胞联合EGFR-TKI治疗35例老年晚期EGFR突变肺癌的效果[J]. 山东大学学报 (医学版), 2022, 60(7): 110-117.

WANG Fuli, SUN Yinping, QIN Jie, RONG Jiansheng. Efficacy of DC-CIK cells combined with EGFR-TKI for 35 elderly patients with advanced EGFR-mutant lung cancer[J]. Journal of Shandong University (Health Sciences), 2022, 60(7): 110-117.

参考文献

[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.

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