Angiogenesis results in the progression, invasion, and metastasis of malignant tumors, and the action of mechanism of apatinib therapy in inhibiting malignancy growth has been confirmed11–13. Compared with placebo group, apatinib could significantly improve the survival time in AGC patients who were refractory to last-line chemotherapy (mPFS: 2.6 months vs 1.8 months; mOS: 6.5 months vs 4.7 months) 14. However, the therapeutic efficacy of apatinib monotherapy was unsatisfactory, which indicated combination therapy getting increasingly applied15. With thousands of years of application and experience, TCM has been widely used in modern society for disease prevention, treatment, and health care. There are increasing interest and investment in the scientific research of TCM among medical and healthcare communities worldwide16. Wu et al. proved that astragalus polysaccharide could inhibit AKT signaling pathway to improve antitumor efficacy of apatinib in gastric cancer AGS cells17. The trial (ChiCTR2100045255) demonstrated that TCM combined with apatinib enhanced the efficacy with tolerable toxicity as the maintenance treatment for patients with extensive-stage small-cell lung cancer (mPFS: 5.0 months; mOS: 18.0 months)18. Based on the fundamental pathogenesis and years of clinical research and mechanism exploration, the previous research results showed that TCM combined with apatinib had the effect of reducing toxicity and increasing efficiency.
XYG combined with apatinib effectively enhanced the clinical efficacy compared with the apatinib group for AGC patients in last-line treatment (mPFS: 6.67 vs 4.00 months; ORR: 46.0% vs 41.0%, P = 0.048; DCR: 82.0% vs 69.0%, P = 0.022). Our study provided clinical evidence for XYG combined with apatinib in the treatment of AGC, which optimized the clinical treatment scheme of integrated TCM and western medicine for AGC patients who failed radiotherapy and chemotherapy. It effectively enhanced the scientific status of TCM in the comprehensive treatment of AGC and provided evidence-based support for the scientific treatment of tumors with TCM. It was significant to promote the complementary and coordinated development of TCM and western medicine, which had a good social demonstration effect and practical application value.
In clinical practice, the team refined the syndrome characteristics and core pathogenesis, created patented prescriptions such as XYG, and explored the application of TCM treatment in the whole management of non-small cell lung cancer. Xiaoyan Decoction participates in radiotherapy and chemotherapy and targeted therapy at different times. It uses "three-dimensional therapy" as a multidisciplinary carrier to standardize individualized and precise treatment of lung cancer. Starting from the overall concept, it stabilizes the tumor lesions and improves immune function. It is an effective adjuvant drug for the treatment of non-small cell lung cancer. Based on clinical efficacy, through basic experimental research, it is preliminarily confirmed that Xiaoyan Decoction inhibits the proliferation, migration, and molecular signaling pathways of lung cancer cells by regulating TGF-β/Smad3/MMP-9, Akt1-mTOR, Beclin1-YAP1 and other molecular signaling pathways19, 20. Besides, it could reverse multidrug resistance, reshape the tumor immune microenvironment, and combine with modern anti-tumor treatment methods to play the role of attenuation and synergy.
According to TCM theory, various components such as Astragali Radix, Hedyotis diffusa, and Prunella vulgaris have effective anti-tumor effects in clinical application. XYG combined with chemotherapy can improve leukocyte toxicity, gastrointestinal nausea, and vomiting symptoms, and significantly improve the quality of life. The possible mechanism of action is to block DA and 5-HT receptors. XYG was used before chemotherapy (the appropriate time was 7 days before chemotherapy) which can significantly reduce the tumor volume and increase the tumor inhibition rate.
The patients selected in this study were relatively standard and representative, which can provide clinical evidence for the clinically integrated traditional Chinese medicine and western medicine regimen of patients with AGC who failed radiotherapy and chemotherapy. Nevertheless, it was still necessary to carry out more prospective clinical studies to further prove the universality of this scheme. The synergistic effect of TCM combined with multitarget antiangiogenic drugs, improving the microenvironment and other related specific mechanisms still needs more in-depth research and discussion. Furthermore, modern molecular biology methods such as network pharmacology and metabolomics can be used to clarify the above problems.