Clinical Effectiveness and Safety of Chinese Herbal Medicine Compound Kushen Injection as an Add-On Treatment for Breast Cancer: A Systematic Review and Meta-Analysis

Abstract

Objective. To systematically evaluate the effect and safety of compound Kushen injection (CKI) as an add-on treatment on the treatment for breast cancer. Methods. We searched eight major electronic databases from their inception to November 1, 2021, for randomized clinical trials (RCTs) comparing CKI plus chemotherapy with chemotherapy alone. Primary outcomes included objective response rate (ORR) and disease control rate (DCR), health-related quality of life (HRQoL), progression-free survival (PFS), and overall survival (OS). Secondary outcomes included adverse drug reactions (ADRs) and tumor marker level. We used Cochrane’s RevMan 5.3 for data analysis. The GRADEpro was used to appraise the certainty of evidence. Trial sequential analysis (TSA) was applied to estimate the required sample size in a meta-analysis and test the robustness of the current results. Results. Thirty RCTs with 2556 participants were totally included. CKI plus chemotherapy showed significant effects in increasing ORR (RR 1.30, 95%CI [1.18, 1.43], I2 = 27%, n = 1694), increasing DCR (RR 1.21, 95%CI [1.15, 1.28], I2 = 16%, n = 1627), increasing HRQol as measured by Karnofsky Performance Scale (KPS) score improvement rate (RR 1.42, 95% CI [1.26, 1.61], I2 = 37%, n = 1172), increasing the PFS (MD 2.24 months, 95%CI [1.26, 3.22], n = 94) and the OS (MD 2.24 months, 95%CI [1.45, 3.43], n = 94), compared to chemotherapy alone. The results showed that CKI plus chemotherapy had a lower risk of ADRs than that of chemotherapy alone group. The certainty of evidence of the included trials was generally low to very low. TSA for ORR and KPS score improvement rate demonstrated that the current results reached a sufficient power regarding both numbers of trials and participants. Conclusions. Low certainty of evidence suggested that the combination of CKI and conventional chemotherapy appeared to improve ORR, DCR, and KPS score in breast cancer patients. Conclusions about PFS and OS could not be drawn due to lack of evidence. Additionally, CKI appeared to relieve the risk of ADRs in patients with breast cancer receiving chemotherapies. However, due to weak evidence, the findings should be further confirmed in large and rigorous trials.

Impact of traditional East Asian medicine as an add-on therapy on survival and recurrence after surgery for breast cancer: A systematic review and meta-analysis

“…However, recent evidence proposes that TEAM used in different stages of cancer lesions might be beneficial to the entire course of cancer prevention and treatment, including recovery from post-operation, and when undergoing radiotherapy or chemotherapy ( Qi et al, 2015 ). Previous studies on the effect of TEAM combined with conventional cancer treatment on postoperative recurrence and survival have been reported in non-small cell lung cancer ( Kawai and Saito, 2020 ), hepatocellular carcinoma ( Zhao et al, 2020 ), bladder cancer ( Chen et al, 2014 ), and breast cancer ( Wang et al, 2015 ; Zhu et al, 2016 ; Ho et al, 2021 ; Lai et al, 2022 ). A phase IB trial conducted in the United States reported that an aqueous extract of S. barbata was well tolerated and showed promising clinical evidence of anticancer activity in patients with metastatic breast cancer ( Perez et al, 2010 ).…”

“…Some studies reported enhanced tumor response, improved quality of life, and reduced risk of adverse events in patients with breast cancer, on evaluating the effects of TEAM combined with chemotherapy compared with chemotherapy alone. However, long-term survival data were unavailable ( Zhu et al, 2016 ; Lai et al, 2022 ). Moreover, most reviews did not separately quantify the clinical benefits of TEAM according to the stage or subtype of breast cancer ( Wang et al, 2015 ; Zhu et al, 2016 ; Ho et al, 2021 ; Lai et al, 2022 ).…”

“…However, long-term survival data were unavailable ( Zhu et al, 2016 ; Lai et al, 2022 ). Moreover, most reviews did not separately quantify the clinical benefits of TEAM according to the stage or subtype of breast cancer ( Wang et al, 2015 ; Zhu et al, 2016 ; Ho et al, 2021 ; Lai et al, 2022 ). Therefore, this systematic review and meta-analysis aimed to synthesize disease-free and overall survival, local and distant control, and toxicity data to analyze the effectiveness and safety of TEAM, as an add-on therapy to standard adjuvant therapy, on survival and recurrence after surgery in patients with stage I–III breast cancer.…”

Compound Kushen injection attenuates angiotensin II‑mediated heart failure by inhibiting the PI3K/Akt pathway

“…The results of a previous study demonstrated numerous pharmacological properties of CKI, including antitumor, analgesic, immunity-enhancing and anti-inflammatory activities ( 14 ). CKI is extensively used in the treatment of numerous malignancies, including breast, lung and liver cancer ( 15 ). CKI is often used alone, or in combination with chemotherapy or radiotherapy ( 16 ).…”

Vascular Protective Effect and Its Possible Mechanism of Action on Selected Active Phytocompounds: A Review

“…Although effective, medications are also associated with adverse effects and cost, as well as challenges with patient compliance [ 7 ]. On the other hand, herbal medicine with adequate clinical effectiveness and low toxicity has been used as an alternative to treat diseases [ 8 , 9 ]. Natural compounds such as flavonoids are becoming increasingly popular.…”