Chinese Herbal Medicine for Improving Quality of Life Among Nonsmall Cell Lung Cancer Patients: Overview of Systematic Reviews and Network Meta-Analysis

Abstract

For patients with nonsmall cell lung cancer (NSCLC) receiving chemotherapy, current clinical evidence has indicated add-on benefit of Chinese herbal medicine (CHM) in improving quality of life (QoL). However, the relative performance among different CHM is unknown. The aim of this overview of systematic reviews (SRs) and network meta-analyses (NMA) is to evaluate the comparative effectiveness of different CHM. Seven electronic databases including both international databases and Chinese databases were searched. SRs focus on randomized controlled trials (RCTs) with comparison of CHM plus chemotherapy against chemotherapy alone on QoL among NSCLC patients were considered eligible. Data from RCTs were extracted for random effect pairwise meta-analyses. Pooled relative risk (RR) with 95% confidence interval (CI) was used to quantify the impact of CHM on QoL. NMA was used to explore the most effective CHM for improving QoL when used with chemotherapy. From 14 SRs, 61 RCTs (n = 4247) assessing 11 different CHM were included. Result from pairwise meta-analyses showed 6 CHM (Kang-lai-te injection, Shei-qi-fu-zheng injection, Compound ku-shen injection, Kang-ai injection, Zi-jin-long tablet, and Shen-fu injection) has significant beneficial effect on QoL among NSCLC patients when used with chemotherapy, even after adjustment for publication bias. Pooled RR varied from 1.38 (95% CI: 1.11-1.72, I2 = 0.0%, Kang-lai-te injection) to 3.36 (95% CI: 1.30-8.66, I2 = 0.0%, Zi-jin-long tablet). One trial comparing Hai-shen-su (a protein extract from Tegillarca granosa L.) plus chemotherapy with chemotherapy also demonstrated beneficial effect of combined treatment (RR = 3.13, 95% CI: 1.41-6.98). Results from NMA showed no differences on the comparative effectiveness among CHM, but Hai-shen-su plus chemotherapy has the highest probability (62.3%) of being the best option for improving QoL. Use of CHM on top of chemotherapy can significantly improve QoL in NSCLC patients. Although Hai-shen-su showed the highest probability of being the best add-on to chemotherapy, the effectiveness of all 11 CHM reviewed appeared to be similar. In the future, rigorous placebo controlled trials with proper blinding are needed to confirm the effectiveness of CHM.

FIGURE 1

Flowchart for literature selection.

FIGURE 2

Risk of bias among included randomized controlled trials.

FIGURE 3

Network of included comparisons. The width of the lines represents the proportion of the number of trials for each comparison to the total number of trials and the size of the nodes represents the proportion of the number of randomized patients (sample sizes). CT = chemotherapy.

FIGURE 4

Comparative effectiveness of 11 Chinese herbal medicines for improving quality of life among nonsmall cell lung cancer patients receiving chemotherapy: Results of indirect comparisons. Results are the relative risks (RRs) and related 95% credibility intervals in the row-defining treatment compared with the RRs in the column-defining treatment. RRs higher than 1 favor the column-defining treatment, and vice versa. Significant results are in bold and are underlined. CT = chemotherapy, FLPD = Fei-liu-ping extract, FZJDD = Fu-zheng-jie-du decoction, HSS = Hai-shen-su, KA = Kang-ai injection, KLT = Kang-la-te injection, KS = Compound Ku-shen injection, SFI = Shen-qi-fu-zheng injection, Shenfu = Shen-fu injection, XAP = Xiao-ai-ping injection, YFBDD = Yi-fei-bai-du decoction, ZLJ = Zi-jin-long tablet.

FIGURE 5

Surface under the cumulative ranking curves (SUCRA) for improving quality of life in nonsmall cell lung cancer patients. The x-axis represents the possible rank of each treatment (from the first best rank to the worst according to the improvement on quality of life). The y-axis indicates the cumulative probability for each treatment to be the best treatment, the second best treatment, the third best treatment, and so on.

FIGURE 6

Funnel plot for assessing publication bias among included randomized controlled trials. RR = relative risk.