Effects of Feiji Recipe in treating non-small cell lung cancer

Wng Tingting(王婷婷), You Jie(游捷), nd Chu Lei(褚磊)

Effects of Feiji Recipe in treating non-small cell lung cancer

Wang Tingting(王婷婷)a, You Jie(游捷)a, and Chu Lei(褚磊)b*

Lung cancer is the leading cause of cancer-related mortality in the world. Although surgery, chemotherapy and radiotherapy can improve the survival rate l, cancers still affect people’s quality of life. Feiji Recipe is an empirical formula and has been used as a treatment for non-small cell lung cancer (NSCLC) for many years. This thesis collects data of the etiology and pathogenesis of Feiji Recipe, clinical research and animal experiments, and provide suggestive evidence of Feiji Recipe for treating NSCLC. During the treatment, the characteristic of holism and personalized treatment of traditional Chinese medicine (TCM) is proved, which also demonstrated that it can relieve patient’s clinical syndrome, improve their quality of life and enhance the body immunity. It plays an irreplaceable role in lung cancer treatment.

Lung cancer; Non-small cell lung cancer; Feiji recipe; Quality of life

Lung cancer is the leading cause of cancer related mortality in the world, accounting for about 19% of all cancer deaths.1It is mainly divided into two types: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). About 85% patients with lung cancers are classified as non-small cell lung cancer (NSCLC) with only 15% overall rate of 5-year survival.2Traditional Chinese medicine (TCM) has the characteristic of holism and personalized treatment, it also has been proved that it can relieve patient’s clinical syndrome, improve their quality of life and enhance the body immunity.3Therefore, it plays an irreplaceable role in lung cancer treatment.

Feiji recipe is an empirical formula from Longhua Hospital, Shanghai University of Traditional Chinese Medicine, and has been used as treatment for NSCLC for many years. The Formulas of Feiji Recipe is as the following: Astragalus 30g, Radix Glehniae 15g, Asparagus 12g, Radix ophiopogonis 12g, Salvia chinensis 30g, Selaginella Doederleinii 30g, herba houttuyniae 15g, Poria cocos 15g, herba epimedii 15g and ect. Our research collected the data on the etiology and pathogenesis of lung cancer, clinical studies and animal experiments of Feiji Recipe, then provided suggestive evidence for treating NSCLC.

ETIOLOGY AND PATHOGENESIS OD LUNG CANCER

There was no appropriate name to define lung cancer in TCM. However, according to its clinical syndrome, lung cancer can be put into “cough”, “lung amassment”,“pulmonary accumulation”, “pulmonary abscess” and “lung carbuncle” category in ancient books. Lung cancer had close correlation with the six exogenous factors, improper diet, former affliction, mental stimulation and age. The lung is compared to the “canopy” because of its uppermost position among all the viscera. The main physiological functions of the lung are to dominate qi and control respiration, govern ascent, dispersion, purification and descent as well as regulate water passage. Lung is a delicate organ and it is susceptible to external affection. Lung mass is formed by Qi-stagnation, blood stasis and retained fluid day by day. General Treatise on the Cause and Symptoms of Medicine has vividly recorded: It was caused by food consumption, retained fluid and blood stasis gradually. At last, people felt fullness and hardness in hypochondrium, swelling pain, shortness of breath. In conclusion, lung clotting was a result of attacking of exogenous evils and internal toxin. Imbalance of yin and yang is the characteristic of the disease.4JingYue encyclopedia has commented: Those who had weaknessof spleen and stomach, deficiency of Qi was prone to suffer from pulmonary accumulation. Another ancient bookZabing Yuanliu Xizhuexplained: Toxin was kept in chest, which blocked the airway and caused lung cancer. Modern physicians also had expressed their opinions on this disease, Pu Bingkui5thought that lung mass was mainly caused by weakness of body and various factors that damage the relative dynamic equilibrium. Ji Guang6insisted that lung cancer was induced by coaction of intrinsic reason and exopathic factor, such as tumor cell toxicity.

In a word, lung cancer was due to insufficient healthy qi and pathogenic factors which damaged the relative equilibrium between yin and yang in the body, or resulted in disturbance of qi and blood, which consequently demonstrated various local and general pathological changes. In brief, it was held that lung cancer was caused by lung Qi deficiency and phlegm and blood stasis , the pathogenesis of which lied in the deficient healthy Qi and excessive pathogenic factors.

CLINICAL APPLICATIONS OD DEIJI RECIP

Relieve clinical syndrome and improve quality of life

Many literatures have pointed out that Feiji Recipe could relieve patients’ clinical symptoms, reduce side effects of chemotherapy and improve their quality of life. You Jie7evaluated the effect of Feiji Recipe on quality of life in patients with NSCLC by adopting International Questionaire of QOL. 102 cases of NSCLC were randomly divided into Feiji Recipe combined with chemotherapy treatment group and chemotherapy treatment group alone. After two course of therapy, QOL in the combined treated group was improved after treatment with the improvement of scores in al l domains, including functional and symptom sub-domain, showing significant difference between the two groups (P＜0.05). Similar results were also shown in the evaluation of physical performance by Eastern Cooperative Oncology Group (ECOG) and Karnovfsky performance scoring. It concluded that Feiji Recipe can improve QOL of patients with NSCLC, reduce the adverse reaction of chemotherapy, and improve patients’ physical performance. Huang Yun sheng8also took Feiji Recipe as a research direction. Patients were randomly divided into two groups after first-line chemotherapeutic regimen, with 30 cases in each group. The patients of the control group received symptomatic treatment, while the other group received Feiji Recipe with regular follow-up. The finding showed that PFS of the treatment group prolonged 1.47 months. There was significant difference between the two groups (P＜0.05). In this regard, Feiji Recipe aslo showed a clearly advantage over extending progression free survival of NSCLC patients. Tian Jin9applied random number table to the study that patients with advanced lung carcinoma were divided into the control group and the therapy group, in which Feiji Recipe was combined with conventional medication. The study had proved the effects of Feiji Recipe on primary NSCLC symptoms.

Reduce side effects of chemotherapy and enhance the body immunity

Huang Yunsheng10divided advanced NSCLC patients with deficiency of Qi and Yin into two groups. The levels of CD4+CD25+Tr, VEGF, sCD44v6, TGF-β1, andiL-10 decreased, in the treatment group as compared with those in the control group respectively. The stabilization rate of tumor in the treatment group was superior to that in the control group (P＜0.05). Improvement of KPS in the treatment group was superior to that in the control group (P＜0.01). They testified that Feiji Recipe could stabilize the tumor body, improve the clinical symptoms of middle stage and advanced NSCLC with Qi -Yin deficiency syndrome, promote patients’ quality of life, and was effective in recovering immune-surveillance and intervening immune escape of lung cancer through multi -pathway to enhance the clinical therapeutic efficacy. Yang Guoliang’s11research demonstrated that improved points on quality of life of the intervention group were better than that of the control group after treatment. The level of CD3+, CD4+, CD4+/CD8+ ration and the NK cell activity was higher than that of the control group. It was suggested that Feiji Recipe combined with chemotherapy could improve the immune function and the quality of life of NSCLC patients. You Jie12also found that Feiji Recipe could reduce side effects of chemotherapy and enhance the body immunity.Huang Yunsheng13and his team put forth the theory that overall response rate of Feiji Recipe group was slightly above the control group, while no statistical difference was found in this comparison (x2=0.073, P=0.787) and all the varying degree had myelosuppression. NCI toxic grading standard differences of two groups had statistical significance (P＜0.05).

EXPERIMENTAL STUDIES

Experimental studies provided the evidence that Feiji Recipe could inhibit tumor cell growth and normalize the vasculature surrounding the tumor. You Jie14made a research that rats with SPAC-1 were randomly divided into blank group and Feiji Recipe groups (small, medium, large dose). The blood vessels in dorsal chamber were observed by confocal microscopy in vivo to calculate the numbers and diameters; the coverage rate of Collagen-IV and a-SMA on vascular wall were observed by immunof l uorescent staining assay. Results on the 5th day after Feiji Recipe intervention showed that the tumor diameter in the large dose of Feiji Recipe group was significantly less than that of the blank group (P＜0.05), on the 9th day after treatment, the vessel number in large and medium dose groups was significantly lower than that of the control group (P＜0.05), and the vessel diameter in the large dose group was significantly lower than that of the medium dose group (P＜0.05), on the 14th day after intervention, the vessel number in the large dose group and medium dose group was significantly lower than that of the control group (P＜0.05) and the tumor diameter in the high dose group was significantly less than that of the control group and small dose group (P＜0.05). The Collagen-iV and a- SMA coverage rate of the vascular tumor was increased from the 6th day after treatment, and the coverage rate in large dose group and medium dose group was significantly higher than that of the blank group (P＜0.05). It had proved that Feiji Recipe can inhibit tumor angiogenesis and normalize tumor vascular. The mechanism may be associated with the improvement of the coverage rates of Collagen-IV and a SMA on vascular. Tian Jianhui15and his group made an observation of the effect of Feiji Recipe on lung cancer metastasis in mice. Twenty-four mice were randomly divided into three groups. Mice in the Feiji Recipe group were treated with Feiji formula decoction; Mice in cisplatin group were treated with cisplatin by intraperitioneal injection; and mice in the untreated group received normal saline. After twenty-day treatment, they found that the body weight of mice in cisplatin group was significantly less than that of Feiji formula group and untreated group (P＜0.01), and the number of metastatic tumors in cisplatin group and Feiji formula group was significantly lower than that of the untreated group (P＜0.01). It testified that Feiji Recipe can suppress tumor growth and decrease the number of lung metastatic tumors in the mice, and maintain the body weight of the mice. You Jie16and her team divided C57 mice and nude mice into the controlled group and decoction groups with low, medium and high dose. The results suggested that Feiji Recipe could restrain the growth of transplantation in lewis lung cancer mice. It reminded us that Feiji Recipe may have certain relation with antiangiogenic agents. Yang Guoliang17designed three groups respectively in detection of the effect of Feiji Recipe combined with chemotherapy on tumor growth, the levels of CD4+CD25+regulatory T cells (Treg) and T lymphocytes in mice with transplanted lewis lung cancer and the underlying mechanism of Feiji Recipe immune evasion. Finally, they found that Feiji Recipe combined with chemotherapy could suppress the growth of lewis lung cancer, which may be involved in decreasing the level of CD4+CD25+Treg.

CONCLUSION

Feiji recipe is mainly composed of Astragalus, Radix Glehniae, Asparagus, Radix ophiopogonis, Salvia chinensis, Selaginella Doederleinii, herba houttuyniae, Poria cocos, herba epimedii and ect. Astragalus can reinforce the vital energy, detoxication and tissue regeneration. Then it is called the sovereign herb of formula. Radix Glehniae, Asparagus and Radix ophiopogonis could nourish lung, spleen and kidney. They are called ministerial drugs. Salvia chinensis, Selaginella Doederleinii, herba houttuyniae are very effective in activating blood circulation to dissipate blood stasis and heat-clearing and detoxifying. A lot of experiments also confirmed the antitumor activityof these herbs. Poria cocos can invigorate the spleen to achieve damp elimination, herba epimedii can strengthen muscles and bones. Research suggested that Feiji Recipe could relieve the clinical syndrome and improve quality of life. Animal experiments also suggested that Feiji Recipe had the effect of inhibiting tumor angiogenesis and normalizing tumor vascular.

第三步是专注客户需求，打造全产业链数字化技术升级。满足客户需求是企业开展一切工作的核心，新一代信息技术为企业获取客户需求提供了便利性。企业要在数字化车间和信息化管理系统的基础上，探索建立面向客户的全产业链服务支持平台，实现智能制造的同时，提供智能在线监测，远程诊断，预防性维护和检修等服务，实现制造型企业数字化转变。

However, many aspects still need further research and more improvement:①Clinical studies and animal experiments of included trails need enlarged samples or reduce the variability of the data. Then it could make the results more reliable.② Trails can adapt the analysis with modified intention to treat and reduce the effect of bias.③Participants who quit the trails should be given follow-up visit, in order to make analysis of studies.④Feiji recipe should make studies on molecular level. It is important to ensure replication and objectivity of trails.

REDERENCES

1 Torre LA, Siegel R, Jemal A. Cancer statistics, Advances in experimental medicine and biology,2016:8931.

2 Mazzone P, Mekhail T. Current and emerging medical treatments for non-small cell lung cancer: a primer for pulmonologists. Respir Med.2012, 106(4):473.

3 Wu wanyin, Wang bin, Zhang haibo. Shenfu Injection on Vinorelbine plus cisplatin for treating advanced non-small cell lung cancer in quality of life. Traditional Chinese Patent Medicine, 2007,29(1):14-18.

4 Ding GuangDi.General Treatise on the Cause and Symptoms of Medicine. Beijing:People's Medical publishing House, 2007:14-18.

5 Zheng Honggang, Hua Baojin. Experience of Pu Bingkui in cure lung cancer with syndrome differentiation and treatment. The journal of Traditional Chinese Medicine, 2010,51(4):304-306.

6 Xu Zhijun. Experience of Ji Gang professor in treating lung cancer. Journal of modern integrated traditional and western medicine, 2010,19(24):3092-3093.

8 Huang Yunsheg. Feiji Recipe maintenance treatment of 30 cases with advanced NSCLC. Jiangxi Journal of Traditional Chinese Medicine,2013,44(362):24-26.

9 Tianjing, Shi Zhiming, et al. Clinical study of Feiji fang treating advanced non-small cell lung cancer.Zhejiang Journal of Traditional Chinese Medicine and Western Medicine, 2006,16(4):201-202.

10 Huang Yunsheng, Shi Zhiming. Intervention effect of Feiji Recipe on immune escape of lung cancer. Chinese journal of integrated traditional and western medicine, 2007,27(6):501-504.

11 Yang guoliang, Zhang xuejin, Hu Dandan. The clinical study on patients with non-small cell lung cancer interfered by Feiji fang combined with chemotherapy. Chinese Archives of Traditional Chinese Medicine, 2011,29(3):663-666.

12 You Jie, Shi Zhiming. Clinical evaluation of Feiji decoction in treating non-small cell lung cancer in 61 cases. Shanghai Journal of Traditional Chinese Medicine, 2005, 39(6):17-20.

13 Huang Yunsheng, Xu Yinglie, Xu Senghua. Treatment for 30 cases with non-small cell lung cancer in Feiji Recipe combined with chemotherapy. Shanxi Journal of Traditional Chinese Medicine, 2015,36(10):1324-1325.

14 You Jie, Zhao Hui, et al. Effect of Feiji prescription on tumor angiogenesis in nude mice with SPAC-1. Shanghai Journal of Traditional Chinese Medicine, 2013,6(47):84-88.

15 Tian Jianhui, Shi Zhiming,et al. Effects on Feiji formula on lung cancer metastasis in mice. Journal of Chinese Integrative Medicine, 2008,6(8):827-829.

16 You Jie, Zhao Hui, et al. Effects of Feiji Recipe on tumor growth in mice with transplanted lewis lung cancer and metastasis. Shanghai Journal of Traditional Chinese Medicine, 2013,27(2):61-64.

17 Yang Guoliang, Zhang Xuejin, Hu dandan. Effects of Feiji fang on levels of CD4+CD5+Treg and T lymphocytes and tumor growth in mice with transplanted lewis lung cancer. Zhejiang Journal of integrated traditional and western medicine, 2013,23(8):605-612.

(Accepted: February 12, 2017)

a: Department of Traditional Chinese Medicine, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200011, China

b: Department of Integrated Traditional and Western Medicine, Tumor hospital of Qingdao, Shandong Province, Qingdao 266042, China

＊Corresponding author: Email: dyjc9105@126.com; Telephone: +86-18561857982