Effectiveness and safety of chemotherapy combined with dendritic cells co-cultured with cytokine-induced killer cells in the treatment of advanced non-small-cell lung cancer: a systematic review and meta-analysis

Abstract

Background: Lung cancer, particularly non-small-cell lung cancer (NSCLC) is the leading cause of cancer mortality. Chemotherapy combined dendritic cells co-cultured with cytokine-induced killer cells (DC-CIK) immunotherapy has been applied in advanced NSCLC patients' treatment, but couldn't provide consistent beneficial results. Therefore, it is necessary to evaluate the efficiency and safety of combination therapy to promote the application.

Methods: A literature search for randomized controlled trials of NSCLC was conducted in PubMed database. Before meta-analysis was performed, studies were evaluated heterogeneity. Pooled risk ratios (RRs) were estimated and 95% confidence intervals (CIs) were calculated using a fixed-effect model. Sensitivity analysis was also performed.

Results: Six eligible trials were enrolled. Efficiency and safety of chemotherapy followed by DC-CIK immunotherapy (experimental group) and chemotherapy alone (control group) were compared. 1-year overall survival (OS) (P = 0.02) and progression free survival (PFS) (P = 0.005) in the experimental group were significantly increased compared with the control. Disease control rate (DCR) (P = 0.006) rose significantly in experimental group. However, no significant differences between the two groups were observed in 2-year OS (P = 0.21), 2-year PFS (P = 0.10), overall response rate (ORR) (P = 0.76) and partial response (PR) (P = 0.22). Temporary fever, anemia, leukopenia and nausea were the four major adverse events (AEs) treated by chemotherapy. The incidence of anemia, leukopenia and nausea in the experimental group was obviously lower than the control group. Temporary fever rate was higher in experimental group than that in the control, but could be alleviated by taking sufficient rest.

Conclusions: Chemotherapy combined with DC-CIK immunotherapy showed superiority in DCR, 1-year OS and PFS, and no more AEs appeared, however, there was no significant improvement in ORR, PR, 2-year OS and PFS. As a whole, the combination therapy is safer but modest in efficacy for advanced NSCLC patients.

Figure 1. Flow diagram.

Figure 2. Forest plot of the comparison of overall survival (OS).

P values are from P for the effect modification evaluation of heterogeneity within or across the groups of regimens. CI, confidence interval; RR, risk ratio; DC/CIK, DC-CIK immunotherapy; Chemo, chemotherapy; Con, control group; Exp, experimental group. A fixed-effect meta-analysis model (Mantel-Haenszel method) was used.

Figure 3. Forest plot of the comparison of progression free survival (PFS).

P values are from P for the effect modification evaluation of heterogeneity within or across the groups of regimens. CI, confidence interval; RR, risk ratio; DC/CIK, DC-CIK immunotherapy; Chemo, chemotherapy; Con, control group; Exp, experimental group. A fixed-effect meta-analysis model (Mantel-Haenszel method) was used.

Figure 4. Forest plot of the comparison of disease control rate (DCR).

P values are from P for the effect modification evaluation of heterogeneity within or across the groups of regimens. CI, confidence interval; RR, risk ratio; DC/CIK, DC-CIK immunotherapy; Chemo, chemotherapy; Con, control group; Exp, experimental group. A fixed-effect meta-analysis model (Mantel-Haenszel method) was used.

Figure 5. Forest plot of the comparison of overall response rate (ORR).

P values are from P for the effect modification evaluation of heterogeneity within or across the groups of regimens. CI, confidence interval; RR, risk ratio; DC/CIK, DC-CIK immunotherapy; Chemo, chemotherapy; Con, control group; Exp, experimental group. A fixed-effect meta-analysis model (Mantel-Haenszel method) was used.

Figure 6. Forest plot of the comparison of partial response rate (PR).

P values are from P for the effect modification evaluation of heterogeneity within or across the groups of regimens. CI, confidence interval; RR, risk ratio; DC/CIK, DC-CIK immunotherapy; Chemo, chemotherapy; Con, control group; Exp, experimental group. A fixed-effect meta-analysis model (Mantel-Haenszel method) was used.