Comparative Efficacy and Safety of Chinese Herbal Injections Combined With Cyclophosphamide and 5-Fluorouracil Chemotherapies in Treatment of Breast Cancer: A Bayesian Network Meta-Analysis

Abstract

Background: Given the limitations of chemotherapy for the treatment of breast cancer (BC) and the wide exploration of Chinese herbal injections (CHIs), this network meta-analysis (NMA) was conducted to analyze the comparative efficacy and safety of nine CHIs combined with CF (Cyclophosphamide and 5-Fluorouracil) chemotherapy regimens in the treatment of BC. Methods: Several electronic databases were searched to identify randomized controlled trials (RCTs) from inception to January 6, 2020. RCTs were screened by pre-established eligibility criteria, and the quality of which was assessed using the Cochrane risk of bias tool. Outcomes such as the clinical effectiveness rate, performance status, peripheral hemogram, and detection of T-lymphocyte subsets were analyzed using the Winbugs 1.4.3 and Stata 13.0 software. Surface under the cumulative ranking curve (SUCRA) probability values were applied to rank the examined treatments. Cluster analysis was performed to compare the effect of CHIs between two or three different outcomes. Results: A total of 84 RCTs involving 7855 patients and nine CHIs were included. The results showed that compared to CF chemotherapy regimens alone, the ones injected along with Aidi, Shenmai, Shenqi Fuzheng, Kangai, Kanglaite, or Shengmai combined with CF can improve the clinical effectiveness rate. Aidi, Shenmai, Shenqi Fuzheng, Compound Kushen, Kangai, and Kanglaite injection combined with CF can improve the performance status. Shenqi Fuzheng injection was considered as a favorable choice for relieving adverse reactions. According to the results of cluster analysis, Aidi injection and Compound Kushen injection plus CF were more favorable for the clinical effectiveness rate and performance status. Conclusion: In conclusion, Shenqi Fuzheng, Compound Kushen, Aidi, and Kangai injection combined with CF chemotherapy regimen have more significant effects for patients with BC. However, more high-quality clinical RCTs, especialy which correctly use blinding and allocation concealment, are required to support the conclusions.

Keywords: Chinese herbal injections; bayesian model; breast cancer; network meta-analysis; randomized controlled trials.

Figure 1

Prisma flow diagram.

Figure 2

Network graph for different outcomes. (A) Clinical effectiveness rate; (B) Performance status; (C) Changes of peripheral blood leukocytes; (D) Peripheral blood platelet changes; (E) CD3⁺; (F) CD4⁺; (G) CD8⁺; (H) CD4+/CD8+. Note: SQFZI, Shenqi Fuzheng injection; CKI, Compound Kushen injection; SMI, Shenmai injection; KAI, Kangai injection; ADI, Aidi injection; KLTI, Kanglaite injection; HQI, Huangqi injection; HCSI, Huachansu injection; SI, Shengmai injection; CF, Cyclophosphamide and 5-Fluorouracil.

Figure 3

Assessment of risk of bias.

Figure 4

Plot of the surface under the cumulative ranking curves for all treatments. (A) Clinical effectiveness rate; (B) Performance status; (C) Changes of peripheral blood leukocytes; (D) Peripheral blood platelet changes; (E) CD3⁺; (F) CD4⁺; (G) CD8⁺; (H) CD4+/CD8+. Note: SQFZI, Shenqi Fuzheng injection; CKI, Compound Kushen injection; SMI, Shenmai injection; KAI, Kangai injection; ADI, Aidi injection; KLTI, Kanglaite injection; HQI, Huangqi injection; HCSI, Huachansu injection; SI, Shengmai injection; CF, Cyclophosphamide and 5-Fluorouracil.

Figure 5

Cluster analysis plot for outcomes. (A) Cluster analysis plot of the Clinical effective rate and Performance status; (B) Cluster analysis plot of the improvement of WBC and PLT; (C) Cluster analysis plot of the Clinical effective rate, improvement of WBC, and Performance status; (D) Cluster analysis plot of the Clinical effective rate, improvement of PLT, and Performance status; (E) Cluster analysis plot of Performance status, improvement of WBC, and PLT; (F) Cluster analysis plot of CD3⁺, CD4+/CD8+, and CD4+. Note: Interventions with the same color belonged to the same cluster, and interventions located in the upper right corner indicate optimal therapy for two different outcomes; SQFZI, Shenqi Fuzheng injection; CKI, Compound Kushen injection; SMI, Shenmai injection; KAI, Kangai injection; ADI, Aidi injection; KLTI, Kanglaite injection; HQI, Huangqi injection; HCSI, Huachansu injection; SI, Shengmai injection; CF, Cyclophosphamide and 5-Fluorouracil.

Figure 6

Funnel plots. (A) Clinical effectiveness rate; (B) Performance status. Note: SQFZI, Shenqi Fuzheng injection; CKI, Compound Kushen injection; SMI, Shenmai injection; KAI, Kangai injection; ADI, Aidi injection; KLTI, Kanglaite injection; HQI, Huangqi injection; HCSI, Huachansu injection; SI, Shengmai injection; CF, Cyclophosphamide and 5-Fluorouracil.