Effectiveness and Safety of Chinese Herbal Injections Combined with Fluoropyrimidine and Oxaliplatin-based Chemotherapy for Advanced Colorectal Cancer: A Systematic Review and Meta-analysis of 63 Randomized Controlled Trials

Purpose: To investigate effectiveness and safety of Chinese herbal injections (CHIs) in conjunction with fluoropyrimidine and oxaliplatin-based chemotherapy (FOBC) for advanced colorectal cancer (CRC). Methods: A comprehensive search was conducted in 7 electronic databases for related randomized controlled trials (RCTs) from inception to April 30, 2021. The quality of each trial was assessed according to the Cochrane Handbook for Systematic Reviews of Interventions, the differences in effectiveness and safety outcomes between two groups were evaluated, and the results were expressed as the risk ratios (RRs) and 95% confidence interval (CI). Subgroup analyses were performed according to the types of CHIs, and Review Manager 5 was used to statistically analyze the outcomes. Results: 63 studies involving 9 CHIs and 4733 patients were included in this review. The meta-analysis results suggested that compared with FOBC therapy, CHIs plus FOBC therapy showed significant improvements in objective response rate (ORR) (RR=1.34, 95% CI: 1.27-1.42, P<0.00001), disease control rate (DCR) (RR=1.09, 95%CI: 1.06-1.11, P<0.00001), 1-year survival rate (RR=2.27, 95% CI: 1.23-4.18, P=0.009) and quality of life (QoL) (RR=1.21, 95% CI: 1.14-1.28, P<0.00001), and decreases in the incidence of chemotherapy-induced leukopenia (RR=0.64, 95% CI: 0.50-0.82, P<0.0005), nausea and vomiting (RR=0.65, 95% CI: 0.51-0.83, P=0.0005) and diarrhea (RR=0.34, 95% CI: 0.20-0.58, P<0.0001). Conclusion: From the evidence available, CHIs could increase ORR, DCR and 1-year survival rate, improve QoL and relieve chemotherapy-induced leukopenia, nausea and vomiting and diarrhea when combined with FOBC in advanced CRC treatment, Nevertheless, on account of the limitations, more rigorous RCTs with high-quality methodology were needed to further confirm the results.