Biological Immune Therapy For Non-small Cell Lung Cancer:a Systematic Review And Meta-analysis

Background:Lung cancer is one of the most common malignancies worldwide and the paramount cause of cancer deaths in the recent twenty years. Non-small cell lung cancer (NSCLC) accounts for approximately85%of all lung cancers. With the development of multidisciplinary treatment methods, surgery, radiotherapy and chemotherapy are all used to treat NSCLC. But its effect on long-term survival is poor in advanced NSCLC, owing to the death for distant metastasis and difficult local control rate. The biological immune treatment of tumor following the surgery, radiotherapy and chemotherapy for fourth mode, the main host defense mechanisms by tumor effect or biological agents to regulate the body’s own biological response, thereby inhibiting or eliminating tumors, it becomes a research focus in future tumor treatment.Objective:To evaluate the clinical efficacy and safety of biological immune therapy for non-small cell lung cancer, and to provide the reference for clinical practice and future research in tumor treatment.Methods:Relevant randomized controlled trials (RCTs) were searched in Cochrane library, Web of Science, PubMed, China Knowledge Resource Integrated Database (CNKI), China Biology Medicine Database (CBM), VIP, and Wan Fang Databases from inception to12February,2014. Meanwhile we searched the dates through other means. RCTs of biological immune therapy for NSCLC were included. We evaluated the quality of these included studies and analyzed date by the Cochrane Collaboration’s RevMan5.1software.Results:The original search identified2050articles in electronic database. We excluded1557studies after review of the title and abstract.493articles were assessed their accordance with the predefined inclusion criteria. Finally,27articles were considered eligible for inclusion in the meta-analysis (1914patients).10articles were published in English and17articles was published in Chinese.(1)16articles reported adoptive cellular immunotherapy for NSCLC. There were594patients in test group, and602in control group. The overall analysis revealed significantly that adoptive cellular immunotherapy improve the overall response rate (OR=1.74,P=0.004,95%CI,1.20-2.52), as well as DC-CIK cell (OR=1.98,P=0.006,95%CI,1.22-3.23).Moreover adoptive cellular immunotherapy could increase1-,2-,3-year overall survival rate(OR＝1.99,P=0.006, 95%CI,1.22-3.25;OR=2.53,P=0.0005,95%CI,1.49-4.28; OR=2.18,P=0.01,95%CI,1.20-3.93), reduced risk of death for overall survival(HR=0.59, P＜0.00001,95%CI,0.47-0.74), and increase immune function(P＜0.05). However, no statistically significant difference was observed for adverse events between groups with adoptive immunotherapy and without adjuvant treatment (P＞0.05).(2)4articles reported interleukin2of cytokine therapy for NSCLC. There were207patients in test group, and193in control group. The overall analysis revealed significantly that interleukin2therapy improve the overall response rate (OR=4.25,P=0.0008,95%CI,1.83-9.89). Unfortunately, interleukin2therapy could not increase1-,2-year overall survival rate (OR=2.93, P=0.15,95%CI,0.68-12.66; OR=1.29,P=0.36,95%CI,0.75-2.23). However, no statistically significant difference was observed for adverse events between groups with interleukin2of cytokine and without adjuvant treatment (P>0.05).(3)2articles reported recombinant adenovirus-p53therapy for NSCLC and5articles for malignant pleural effusion. There were38NSCLC patients in test group, and38in control group; and121malignant pleural effusion patients in test group, and121in control group. The overall analysis revealed significantly that recombinant adenovirus-p53therapy improve the overall response rate in treating NSCLC (OR=4.93, P=0.03,95%CI,1.17-20.75) and malignant pleural effusion (OR=3.35,P＜0.0001,95%CI,1.91-5.89). Unfortunately, recombinant adenovirus-p53therapy could not increase1-year overall survival rate (OR=1.25, P=0.72,95%CI,0.36-4.32). There was no statistically significant difference of adverse events (P＞0.05) but fever in NSCLC patients receiving interleukin2(OR=11.81,P＝0.002,95%CI,2.55-54.68).Conclusion:biological immune therapy with surgery, chemotherapy and radiotherapy could improve the therapeutic effect for non-small cell lung cancer. But as a new treatment at present, there were lack of the large sample and rigorous clinical research data of long follow-up. Thus, long-term efficacy, adverse events, administration methods, timing and the efficacy of different cell types should be further explored; and the preparation process of biological drugs, the combination treatment strategies should be further standardized and unified.