Gefitinib plus Fuzheng Kang'ai Formula(扶正抗癌方) in Patients with Advanced Non-Small Cell Lung Cancer with Epidermal Growth Factor Receptor Mutation:A Randomized Controlled Trial

Objective： To evaluate the effect of Fuzheng Kang＇ai Formula （扶正抗癌方, FZKA） plus gefitinib in patients with advanced non-small cell lung cancer with epidermal growth factor receptor （EGFR） mutations. Methods： A randomized controlled trial was conducted from 2009 to 2012 in South China. Seventy chemotherapynaive patients diagnosed with stage ⅢB/Ⅳ non-small cell lung cancer with EGFR mutations were randomly assigned to GF group [gefitinib （250 mg/day orally） plus FZKA （250 mL, twice per day, orally）; 35 cases] or G group （gefitinib 250 mg/day orally; 35 cases） according to the random number table and received treatment until progression of the disease, or development of unacceptable toxicities. The primary endpoint [progression-free survival （PFS）] and secondary endpoints [median survival time （MST）, objective response rate （ORR）, disease control rate （DCR） and safety] were observed. Results： No patient was excluded after randomization. GF group had significantly longer PFS and MST compared with the G group, with median PFS of 12.5 months （95% CI 3.30-21.69） vs. 8.4 months （95% CI 6.30-10.50; log-rank P〈0.01）, MST of 21.5 months （95% CI 17.28-25.73） vs. 18.3 months （95% CI 17.97-18.63; log-rank P〈0.01）. ORR and DCR in GF group and G group were 65.7% vs. 57.1%, 94.3% vs. 80.0%, respectively （P〉0.05）. The most common toxic effects in the GF group and G group were rash or acne （42.8% vs. 57.1%, P〉0.05）, diarrhea （11.5% vs. 31.4%, P〈0.05）, and stomatitis （2.9% vs. 8.7%, P〉0.05）. Conclusion： Patients with advanced non-small cell lung cancer selected by EGFR mutations have longer PFS, MST with less toxicity treated with gefitinib plus FZKA than gefitinib alone.

Mechanism of Fuzheng Kang'ai Formula Regulating Tumor Microenvironment in Non-Small Cell Lung Cancer

Objective:To study the mechanism of Chinese herbal medicine Fuzheng Kang’ai Formula(FZKA)on tumor microenvironment(TME).Methods:CIBERSORTx was used for analysis of TME.Traditional Chinese Medicine Systems Pharmacology and Analysis Platform was applied to identify compounds-targets network and the Cancer Genome Atlas(TCGA)was employed to identify the differential expression genes(DEGs)between tumor and paracancerous tissues in lung adenocarcinoma(LUAD)from TCGA-LUAD.Additionally,DEGs with prognosis in LUAD was calculated by univariable and multivariate Cox regression.The core targets of FZKA were analyzed in lung adenocarcinoma TME.Protein-protein interaction database was employed to predict down-stream of target.Quantitative reverse transcription polymerase chain reaction was employed for biological experiment in A549,H1299 and PC9 cell lines.Results:The active and resting mast cells were significantly associated with prognosis of LUAD(P<0.05).Of the targets,CCNA2 as an important target of FZKA(hazard ratio=1.41,95%confidential interval:1.01-2.01,P<0.05)was a prognostic target and significantly associated with mast cells.CCNA2 was positively correlated with mast cell activation and negatively correlated with mast cell resting state.BCL1 L2,ACTL6 A and ITGAV were down-stream of CCNA2,which were validated by q RT-PCR in A549 cell.Conclusion:FZKA could directly bind to CCNA2 and inhibit tumor growth by regulating CCNA2 downstream genes and TME of NSCLC closely related to CCNA2.

扶正抗癌方治疗晚期非小细胞肺癌疗效的Meta分析

目的探讨扶正抗癌方联合化疗治疗晚期非小细胞肺癌(NSCLC)的疗效和安全性。方法在中国生物医学文献数据库、Pub Med等数据库检索扶正抗癌方联合化疗治疗晚期NSCLC的随机对照试验(RCT),采用Meta分析专用软件Rev Man 5.2进行系统评价。结果共纳入6个RCT,均为B级文献,共有467例NSCLC患者。Meta分析显示,扶正抗癌方联合化疗治疗晚期NSCLC的有效率优于单纯化疗组,差异有统计学意义[RR=1.87,95%CI(1.28~2.72)];扶正抗癌方联合化疗组的不良反应发生率低于单纯化疗组,差异有统计学意义[RR=0.29,95%CI(0.16~0.54)]。研究无明显发表偏倚。结论现有研究表明,扶正抗癌方联合化疗治疗晚期NSCLC的有效率优于单纯化疗组,且安全性更佳。