Efficacy and Safety of Cinobufacin Combined with Chemotherapy for Advanced Breast Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: Cinobufacin is a Chinese patent medicine widely used for breast cancer in China. However, no systematic review and meta-analysis have been published to validate its effects in breast cancer treatment. We, therefore, summarize the efficacy and safety of Cinobufacin combined with chemotherapy in order to provide rigid evidence for its clinical application. METHODS: By searching multiple databases incepted to December 2019, the RCTs of breast cancer patients treated with Cinobufacin were screened according to the inclusion criteria, and the meta-analysis and sensitivity analysis were conducted using RevMan5.3. RESULTS: A total of 1163 articles were retrieved, and 16 studies were included. The total sample size was 1331 cases, including 666 cases in the treatment group receiving Cinobufacin combined with chemotherapy and 665 cases in the control group receiving chemotherapy alone. Our study found that the ORR (overall response rate) (RR = 1.35, 95% CI: [1.23, 1.49], P < 0.00001), CBR (clinical benefit rate) (RR = 1.14, 95% CI: [1.08, 1.21], P < 0.00001), KPS scores (RR = 1.98, 95% CI: [1.45, 2.68], P < 0.0001), and pain relief rate (RR = 1.34, 95% CI: [1.01, 1.78] P=0.04 of the Cinobufacin combined with chemotherapy group were better than those of the chemotherapy group, and the difference was statistically significant. Our study also discovered that the tumor markers (CA125, CA153, and CEA) in the Cinobufacin combined with chemotherapy group were lower than those in the chemotherapy group, which heterogeneity was derived from the low-quality literature included in the study, but the results were robust. In addition, in terms of safety, we found that the incidences of gastrointestinal reactions (RR = 0.58, 95% CI: [0.48, 0.70], P < 0.00001), liver and kidney damage (RR = 0.57, 95% CI: [0.38, 0.84], P=0.004), and hair loss (RR = 0.61, 95% CI: [0.40, 0.92], P=0.02) in the Cinobufacin combined chemotherapy group were lower than those in the chemotherapy group