4. Discussion
At present, western medicine is the main treatment for lung cancer. Western medicine plays a role in directly fighting against cancer cells. While, traditional Chinese medicines (TCMs) for cancer treatment often plays a multi-target or multi-effect therapeutic role[66]. There are many aspects in the treatment of cancer with TCMs, such as enhancing the inhibitory effect on cancer cells, inhibiting the angiogenesis of tumors, and reversing the effect of drug resistance targeting. Shu Q, et al[67] found that aqueous extract of Taxus chinensis in combination with erlotinib inhibits the proliferation of cancer cells by inhibiting the expression of P-EGFR, P-ERK, and P-JNK proteins in the EGFR/MAPK signaling pathway. Kou J, et al[68] found that Xiaoaiping combined with hyperthermia could inhibit the proliferation of gefitinib-resistant human lung adenocarcinoma A549 cell line by reducing the expression of vascular endothelial growth factor and mediating angiogenesis. Gao F,et al [69] found that β-elemene can reverse PC9/ZD resistance, which probably is related with its down-regulation of p-Erk and p-Akt protein expression.
Molecular targeted therapy has been recognized as one of the effective methods to treat some cancer types. The Food and Drug Administration has tested and approved EGFR-TKIs as molecularly targeted agents for the treatment of non-small cell lung cancer, mainly including the First-generation drug gefitinib (Iressa, 2003) and Erlotinib (Tarceva, 2004); The Second generation drug Afatinib (Afatinib, Gilotrif, 2013), and the third generation of drugs for Osimertinib (Osimertinib, Tagrisso, 2015). At present, thousands of studies have demonstrated the effectiveness of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) as molecular targeted agents[70, 71]. Many studies have now shown that epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have multidrug resistance mechanisms in EGFR-mutated non-small cell lung cancer (NSCLC). Nevertheless, relapsed drug resistance in EGFR-TKIs remains a major clinical challenge due to heterogeneous mechanisms [72]. Because of the high cost of treatment and the lack of relevant clinical research results, in particular, there are few research cases of combined application of TCM. To explore the clinical basis of adding TCMs to EGFR-TKIs in the treatment of non-small cell lung cancer, our study evaluated 57 studies that were classified as capsule group (7studies), granule group (2 studies), decoction group (22 studies), TCM differentiation group (5 studies) and injection group (21 studies), which had 4266 experimental subjects, 2161 in the experimental group and 2105 in the control group. In this study, TCM or TCM plus EGFR-TKIs in the treatment of NSCLC get the better of EGFR-TKIs solely in terms of short-term efficiency and long-term survival rate, reflecting the synergistic effect of TCM-assisted EGFR-TKIs treatment. The principle of treatment is to strengthen the body and remove pathogenic factors. The diseases of zang-fu organs are mainly located in the lung, spleen and stomach, and heart and kidney. The treatment mostly adopts flexible compatibility and cutting methods, which can be roughly divided into the following categories: (1) Tonifying qi and yin: shashen, maidong, huangqi, renshen and so on; (2) Heat-clearing and detoxifying: baihuashecao, daqingye, shancigu, lianqiao and so on; (3) Dispelling wind and arresting itching: fangfeng, jiangcan, chantui, baixianpi, difuzi and so on; (4) Promoting circulation and removing stasis: danshen, chishao, yujin, taoren, honghua, eshu and so on; (5) Clearing damp phlegm: chenpi, banxia, fuling, baishu and so on.
Taken together, we have demonstrated that particular combinations of TCMs with EGFR-TKIs have a greater effect on TRR than EGFR-TKIs alone. Among them, it is worth noticing combination of Maidong, Baihuashecao, Shashen, Renshen and Dangshen. Therefore, TCM may have the potential to improve the efficacy of EGFR-TKI in the treatment of lung cancer. However, the limitations of this study are also obvious, such as almost all the selected studies are in Chinese literature, the lack of rigorous design and implementation, and the low quality of research, which affect the accuracy and reliability of the conclusions of this study to a certain extent.