Efficacy and safety of oral Chinese medicine combined with chemotherapy: A Systematic Review and Network Meta-analysis

Yuqi MaJia LiLiyun Liu^*Tao Shen^*

• School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China, Chengdu, China

Abstract Background: Non-small cell lung cancer (NSCLC), a leading cause of global cancer mortality, often presents at advanced stages with limited efficacy from standard chemotherapy. This study evaluated the efficacy and safety of six oral Chinese medicines (TCMs) combined with chemotherapy for NSCLC. Methods: Following PRISMA-NMA guidelines, a systematic review and network meta-analysis of 36 randomized controlled trials (RCTs, n=2,846 patients) was conducted. Databases including PubMed, CNKI, and Web of Science were searched. Outcomes assessed included objective response rate (ORR), immune markers (CD4-CD8 ratio, NK cells), tumor markers (CA125, CEA, CYFRA21-1), and adverse events. Data were synthesized using Stata 14.0 and R software, with risk of bias evaluated via Cochrane RoB 2.0. Results: Compared to chemotherapy alone, Tongguanteng (TGT, Marsdenia tenacissima) demonstrated superior improvement in objective response rate (ORR) [OR = 1.88, 95% CI: 1.25–2.83]. This effect may be attributable to its vincristine content, which modulates apoptosis through cell cycle regulation pathways. Huisheng (HS) ranked second in efficacy [OR = 1.34, 95% CI: 1.10–1.61], with its emodin component suppressing NSCLC proliferation via NF-κB pathway inhibition. HS was associated with immune markers, including CD4+/CD8+ ratio and natural killer (NK) cell activity. Conversely, TGT significantly reduced tumor markers: CA125, carcinoembryonic antigen (CEA), and cytokeratin-19 fragment (CYFRA21-1). The latter observation may align with tenacissoside’s inhibition of cytochrome P450 enzymes (CYP2D6/CYP3A4), which alter drug metabolism. While TCMs-chemotherapy combinations exhibited improved safety profiles compared to chemotherapy alone, the analysis revealed potential publication bias and moderate heterogeneity. Conclusion: HS and TGT, potentially through their bioactive components, may enhance chemotherapy efficacy in NSCLC by targeting immune and metabolic pathways. However, these conclusions need further verification. Findings should be interpreted cautiously due to potential bias, limited RCTs, and geographical concentration of studies. Future research should isolate compound-specific effects and validate mechanisms in global trials.