Adjuvant Chemotherapy with Chinese Herbal Medicine Formulas Versus Placebo in Patients with Lung Adenocarcinoma after Radical Surgery: a Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: The toxicity and side effects caused by adjuvant chemotherapy (ACT) after radical surgery for lung adenocarcinoma (LAC) lead to early termination frequently. This study was conducted to provide an objective basis for the effect of Chinese herbal medicine formulas (CHMFs) combined with chemotherapy in reducing toxicity and enhancing efficacy of ACT. METHOD: From February 17th, 2012 to March 20th, 2015, 233 patients from 7 hospitals diagnosed with LAC in IB~IIIA stage were randomly assigned into ACT + CHMF group (116 patients) and ACT + placebo group (117 patients). CHMF was taken orally until the end of chemotherapy. Chemotherapy-related toxic, side effects were investigated as the primary outcome. Disease-free survival (DFS) and overall survival (OS) were used as the secondary outcome. RESULTS: At one week following chemotherapy, the incidence of dry mouth, diarrhea and thrombocytopenia significantly decreased in CHMF group (P = 0.017, P = 0.033, P = 0.019, respectively). At two weeks following chemotherapy, fatigue and diarrhea were more obvious in the placebo group (P = 0.028, P = 0.025, respectively). In addition, patients in the CHMF group showed an increase in median DFS from 37.1 to 51.5 months compared with placebo group although there was no statistical significance (P = 0.16). In the stage IB subgroup, the CHMF group had a significantly better DFS (HR (95% CI) = 0.53 (0.28-0.99), P = 0.046). There was no significant difference in OS between the groups (P = 0.72). CONCLUSION: For patients with LAC, ACT combined with CHMF after radical surgery can prolong the DFS time especially in the early stage, and reduces the chemotherapy-related toxic and side effects. TRIAL REGISTRATION: NCT01441752. Registered 14 July, 2011.

Chinese Herbal Medicine Combined With EGFR-TKI in EGFR Mutation-Positive Advanced Pulmonary Adenocarcinoma (CATLA): A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial.

Background: To determine the clinical activity and safety of Chinese herbal medicine (CHM) combined with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) in patients with advanced pulmonary adenocarcinoma (ADC) and the ability of CHM combined with EGFR-TKI to activate EGFR mutations. Methods: Three hundred and fifty-four patients were randomly assigned to EGFR-TKI (erlotinib 150 mg/d, gefitinib 250 mg/d, or icotinib 125 mg tid/d) plus CHM (TKI+CHM, N = 185) or EGFR-TKI plus placebo (TKI+placebo, N = 169). Progression-free survival (PFS) was the primary end point; the secondary end points were overall survival (OS), objective response rate (ORR), disease control rate (DCR), quality of life [Functional Assessment of Cancer Therapy-Lung (FACT-L) and Lung Cancer Symptom Scale (LCSS)], and safety. Results: The median PFS was significantly longer for the TKI+CHM group (13.50 months; 95% CI, 11.20-16.46 months) than with the EGFR-TKI group (10.94 months; 95% CI, 8.97-12.45 months; hazard ratio, 0.68; 95% CI, 0.51-0.90; P = 0.0064). The subgroup analyses favored TKI+CHM as a first-line treatment (15.97 vs. 10.97 months, P = 0.0447) rather than as a second-line treatment (11.43 vs. 9.23 months, P = 0.0530). Patients with exon 19 deletion had a significantly longer PFS than with 21 L858R. The addition of CHM to TKI significantly improved the ORR (64.32% vs. 52.66%, P = 0.026) and QoL. Drug-related grade 1-2 adverse events were less common with TKI+CHM. Conclusions: TKI+CHM improved PFS when compared with TKI alone in patients with EGFR mutation-positive advanced non-small-cell lung cancer (NSCLC). Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT01745302.

Maintenance Chemotherapy With Chinese Herb Medicine Formulas vs. With Placebo in Patients With Advanced Non-small Cell Lung Cancer After First-Line Chemotherapy: A Multicenter, Randomized, Double-Blind Trial.

Background: Chinese Herb Medicine Formulas (CHMF) was reported to improve the quality of life (QoL) in advanced NSCLC patients. The present study was designed to investigate whether maintenance chemotherapy plus CHMF in patients would improve QoL and progression-free survival (PFS). Methods: Seventy-one patients were enrolled from 8 medical centers in China, and were randomly assigned to a maintenance chemotherapy plus CHMF group (n = 35) or a maintenance chemotherapy plus placebo group (n = 36). The outcome measures included PFS, Karnofsky performance status (KPS) scores, QoL (assessed with the lung cancer symptom scale (LCSS) questionnaire), and adverse events (AEs). Results: Patients in the CHMF group showed significant improvements in median PFS (HR = 0.55, 95% CI 0.28-0.88, P = 0.019), KPS scores (P = 0.047), fatigue (cycle [C] 3: P = 0.03), interference with daily activities (C3: P = 0.04) and dyspnea (C2: P = 0.03) compared with patients in the placebo group. Compared with the placebo group, the incidence of AEs decreased in the CHMF group, including loss of appetite (C2: P = 0.011, C4: P = 0.004) and dry mouth (C4: P = 0.011). Conclusion: The essential finding of our study is that maintenance chemotherapy combined with CHMF may prolong PFS, relieve symptoms, improve QoL and alleviate the side effects.

Associations between polymorphisms of long non-coding RNA MEG3 and risk of colorectal cancer in Chinese.

Maternally expressed gene 3 (MEG3), a long non-coding RNA (lncRNA), is involved in cancer development and metastasis. The objective of the present study was to evaluate whether common single nucleotide polymorphisms (SNPs) in MEG3 could be related with colorectal cancer risk in Chinese. We genotyped six tagSNPs of MEG3 in a colorectal cancer case-control study including 518 cases and 527 control subjects. Multivariate logistic regression analysis was applied to calculate adjusted odds ratios (ORs). We found that MEG3 rs7158663 AA genotype, but not GA genotype, had significant increased colorectal cancer risk, compared with GG genotype (OR = 1.96 and P = 0.006 for AA versus GG, and OR = 1.20 and P = 0.171 for GA versus GG). Further stratified analysis indicated that the increased risk was significantly correlated with individuals with age ≤ 60 and family history of cancer. However, there was no significant association between rs7158663 and colorectal tumor site and stage (P = 0.842 for tumor site, and P = 0.601 for tumor stage). These results demonstrate that genetic variants in MEG3 may contribute to the development and risk of colorectal cancer. Further studies are required to confirm these findings.

Association of the SNP rs1800925(C/T) in the interleukin-13 gene promoter with pulmonary function in Chinese Han patients with idiopathic pulmonary fibrosis.

The present report studied potential association of the rs1800925(C/T) single nucleotide polymorphism (SNP) of the Interleukin (IL)-13 gene promoter with idiopathic pulmonary fibrosis (IPF) in patients of Chinese Han ethnicity. Seventy patients with IPF were enrolled and divided into three subgroups: group A (61-79 % pred. DLCO; n = 22), group B (51-60% pred. DLCO; n = 20), and group C (≤50% pred. DLCO; n = 28). Control group consisted of 80 healthy individuals of Chinese Han ethnicity. The SNP rs1800925(C/T) was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. The IL-13 CC genotype was present in 28/70 (40.0%), homozygous TT in 6/70 (8.6%) and heterozygous CT in 36/70 (51.4%) patients with IPF. In control group, these genotypes were present in 30/80 (37.5%), 11/80 (13.75%), 39/80 (48.75%), respectively, indicating that the distribution of the above three genotypes was not significantly different between patients with IPF and healthy controls. When the patients were stratified according to their DLCO and DLCO/VA, the frequencies of genotypes CT and TT in the groups A, B, and C were, respectively, 40.9% (9/22), 50% (10/20), and 82.1% (23/28). Thus, significant differences in the distribution of alleles at -1112 region of IL-13 gene were observed among the study groups A, B, and C, with the highest frequency in group C (p < 0.05). In conclusion, the rs1800925 T allele of the IL-13 gene is associated with worse pulmonary function in patients with IPF of Chinese Han ethnicity.

[Curative effect of 3D-CRT combined with gemcitabine concurrently with addition of Kanglaite Injection in treatment of locally advanced pancreatic].

OBJECTIVE: To explore the efficacy of concurrent chemoradiotherapy combined with Kanglaite Injection (KI) for locally advanced pancreatic carcinoma patients. METHODS: Totally 50 patients unsuitable for surgery were randomly assigned to the treatment group and the control group, 25 in each group. Patients in the control group were treated with gemcitabine and concurrent 3D-CRT, while those in the treatment group were also treated with intravenous injection of KI (at 100 mL/d) for 21 successive days, 28 days as one cycle, two cycles with one week interval. The short-term curative effect, the survival time, the improvement of symptoms, the tumor markers, and adverse reactions were respectively observed for two years. RESULTS: The short-term curative effective rate (CR + PR) was 52.17% (12/23), and the disease control rate (CR + PR + SD) was 95.65% (22/23) in the treatment group. The short-term curative effective rate (CR + PR) was 41.67% (10/24), and the disease control rate (CR + PR + SD) was 87.50% (21/24) in the control group. There was no statistical difference between the two groups (P > 0.05). The 2-year survival rate was 34.78% (8/23) in the treatment group, better than that in the control group (25.00%, 6/24). The median survival time was 17.2 months in the treatment group and 12.4 months in the control group with statistical difference (P < 0.05). The response rate of pain relief and weight gain were 75.00% and 82.61% in the treatment group respectively, and they were 50.00% and 54.67% in the control group respectively, showing statistical difference between the two groups (P < 0.05). After treatment, the levels of CA19-9 (U/mL) and CEA (ng/mL) were respectively reduced to 118. 00 +/- 78.89 and 7.41 +/- 2.37 respectively in the treatment group, showing statistical difference when compared with those of the control group (being 216.00 +/- 153.23 and 12.25 +/- 7.53 respectively, P < 0.05). CONCLUSION: The concurrent chemoradiotherapy com- bined with KI for locally advanced pancreatic carcinoma patients obtained better results.

Protective effects of salidroside on epirubicin-induced early left ventricular regional systolic dysfunction in patients with breast cancer.

BACKGROUND: Salidroside [2-(4-hydroxyphenyl)ethyl-ß-D-glucopyranoside], one of the most potent ingredients extracted from the plant Rhodiola rosea L., has been shown to have a cardiovascular protective effect as an antioxidant, and early treatment of epirubicin-induced cardiotoxicity has been the focus of clinical chemotherapy in patients with breast cancer. However, the cardioprotective effects of salidroside on epirubicin-induced cardiotoxicity, especially early left ventricular regional systolic dysfunction, have to date been sparsely investigated. OBJECTIVE: The aim of this study was to investigate the protective effects of salidroside in preventing early left ventricular regional systolic dysfunction induced by epirubicin. METHODS: Sixty patients with histologically confirmed breast cancer were enrolled. Eligible patients were randomized to receive salidroside (600 mg/day; n = 30) or placebo (n = 30) starting 1 week before chemotherapy. Patients were investigated by means of echocardiography and strain rate (SR) imaging. We also measured plasma concentrations of reactive oxygen species (ROS). All parameters were assessed at baseline and 7 days after each new epirubicin dose of 100 mg/m2. RESULTS: A decline of the SR peak was observed at an epirubicin dose of 200 mg/m2, with no significant differences between salidroside and placebo (1.35 ± 0.36 vs 1.42 ± 0.49/second). At growing cumulative doses of epirubicin, the SR normalized only with salidroside, showing a significant difference in comparison with placebo at epirubicin doses of 300 mg/m2 (1.67 ± 0.43 vs 1.32 ± 0.53/second, p < 0.05) and 400 mg/m2 (1.68 ± 0.29 vs 1.40 ± 0.23/second, p < 0.05). Moreover, a significant increase in plasma concentrations of ROS was found with placebo, but they remained unchanged with salidroside. CONCLUSION: Salidroside can provide a protective effect on epirubicin-induced early left ventricular regional systolic dysfunction in patients with breast cancer.

CXCL12 G801A polymorphism and breast cancer risk: a meta-analysis.

The G801A polymorphism in the CXCL12 gene has been implicated in breast cancer risk. However, the published findings are inconsistent. We therefore performed a meta-analysis to investigate this relationship. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the association. The pooled ORs were performed for codominant model, dominant model, and recessive model, respectively. Five published case-control studies, including 1,058 breast cancer cases and 1,023 controls were identified. No study had a deviation from the Hardy-Weinberg equilibrium (HWE) in controls. We found that the CXCL12 G801A (rs1801157) polymorphism was associated with a significantly increased risk of breast cancer risk when all studies were pooled into the meta-analysis (codomiant model: AA versus GG, OR = 1.64, 95% CI = 1.16-2.33; GA versus GG, OR = 1.42, 95% CI = 1.18-1.71; dominant model: AA/GA versus GG, OR = 1.44, 95% CI = 1.21-1.72). Furthermore, Egger's test did not show any evidence of publication bias (P > 0.05 for the dominant model). In conclusion, the results suggest that the CXCL12 G801A polymorphism may be a low-penetrant risk factor for developing breast cancer.

[Effect of rhodiola on serum troponin 1, cardiac integral backscatter and left ventricle ejective fraction of patients who received epirubicin-contained chemotherapy].

OBJECTIVE: To investigate the myocardial protective effect of Rhodiola on patients who received epidoxorubicin (EPI) treatment. METHODS: Forty-two patients with myocardial damage who received 3 courses of EPI-contained chemotherapy were randomly and equally assigned to two groups, the Rhodiola treated group and the control group. After 1-month treatment, the changes in serum troponin I (cTnI) level, cardiac integral backscatter (IBS), and left ventricle ejective fraction (LVEF) in patients were observed and compared between groups. RESULTS: Levels of cTnI in the treated group and control group were (0.54 +/- 0.05) mg/L and (0.98 +/- 0.03) mg/L respectively, IBS were 55.23 +/- 5.72 scores and 61.23 +/- 5.96 scores, and LVEF (%) were 68 +/- 3 and 57 +/- 2 respectively, all showed significant differences between groups (P<0.05). CONCLUSION: Rhodiola can improve cardiac function, and suppress the increase of serum cTnI level and IBS in patients who received EPI treatment.

The protective effects of ambroxol on radiation lung injury and influence on production of transforming growth factor beta1 and tumor necrosis factor alpha.

The aim of this article was to investigate the effect of ambroxol on radiation lung injury and the expression of transforming growth factor beta(1) (TGF-beta(1)), as well as tumor necrosis factor alpha (TNF-alpha) in plasma. Totally, 120 patients with locally advanced lung cancer in radiotherapy were randomized into treatment and control groups. Patients in the treatment group took ambroxol orally at a dosage of 90 mg, three times per day for 3 months from the beginning of radiotherapy. The expression of TGF-beta(1) and TNF-alpha in plasma was analyzed. The clinical symptoms and lung diffusing capacity were monitored using high resolving power computed tomography. The level of TGF-beta(1) in the control group was increased (11.8 +/- 5.5 ng/ml), whereas in ambroxol-treated patients, the increase was not significant (5.6 +/- 2.6 ng/ml, P < 0.001). Radiotherapy-induced elevation of TNF-alpha levels, seen in control patients, was also abolished after treatment with ambroxol (5.1 +/- 1.0 vs. 2.4 +/- 0.8 ng/ml, P < 0.001). In the treatment group, carbon monoxide diffusion capacity was not significantly decreased at 6, 12, and 18 months post-radiotherapy, compared with the control group (P < 0.05). Ambroxol decreased the expression of TGF-beta(1) and TNF-alpha, and minimized the diminishment of lung diffusion capacity after radiotherapy.

[The clinical study on chronic hepatitis B treated by the four-step therapeutics of Traditional Chinese Medicine].

OBJECTIVE: To observe the clinical curative effect of chronic hepatitis B treated by the four-step therapeutics of Traditional Chinese Medicine (TCM). METHODS: 120 patients with mild or moderate Chronic Hepatitis B (CHB) were randomly divided into two groups: 80 patients in treatment group and 40 in control group. All enrolled cases accorded with the enroll standard. In treatment group, the patients were divided into mild moderate and severe degree of immune intervention based on the ALT level and treated with four-step therapeutics according to the dialectical theory. In control group, all patients were administered 100mg Lamivudine orally daily for two years. RESULTS: The loss rates of HBeAg, HBV-DNA, precore mutation were 58.9%, 78.9% in treatment group respectively, and 33.3%, 38.9% in control group. There were significant defferences between them. The total effectiveness ratio of two groups has no significant difference. After the treatment, the value of HA, PCIII, IV. C,LN decreased dramatically in treatment group and the antihepatic fibrosis results of treatment group were superior to those of control group. The four-step therapeutics of TCM could improve the ALT value and the ALT value declined to normal after the virus indexes' loss. The response rate in treatment group of ALT-elevating patients was higher than those of no ALT- elevating patients. CONCLUSION: The four-step therapeutics of TCM is effective in treating the CHB patients.

Two-year observation of the clinical efficacy in treating chronic hepatitis B Patients with Ganxian recipe and lamivudine.

OBJECTIVE: To evaluate the clinical efficacy of Ganxian recipe (GXR) and lamivudine (LVD) in a two-year treatment of chronic hepatitis B (CHB). METHODS: One hundred and twenty patients with CHB were randomly divided into the combinedly treated group (combined group) of 40 CHB patients who were treated with GXR combined with LVD. Another 40 CHB patients were treated with LVD alone (WM group), and still another 40 CHB patients were treated with GXR alone (TCM group). All these cases were randomly controlled and observed for two years. RESULTS: Comprehensive efficacy: Total effective rate of the combined group (complete response and partial response) was 92.5%, while that of the WM group was 67.5% and TCM group 57.5%, respectively, with the difference between them was significant (P < 0.01); after treatment, the hepatic functions (AST, ALT, SB) of the three groups were all reduced, and the reduction in the combined group was particularly significant in comparison with the WM group or TCM group, P < 0.05 or P < 0.01 respectively, suggesting that the effect in the combined group was better than that in the other two groups; the rate of tyrosine-methionine-aspartate-aspartate (YMDD) virus mutation: it was 7.5% in the combined group, 40.0% in the WM group, and 5.0% in the TCM group; liver fibrosis improvement parameter: after treatment, the results in the combined group got better than those in the other two groups. CONCLUSION: GXR could inhibit the appearance of YMDD after long-term application of LVD, and combined use has marked synergism.

[Clinical observation of the treatment of 654-2 injection and "ganxian tui huang recipe" on liver cirrhosis with intractable jaundice].

OBJECTIVE: To observe the effect of 654-2 injection and "GanXian Tui Huang Recipe" on hepatic fibrosis with intractable jaundice. METHODS: 60 patients were treated for 3 months and randomly divided into control group and experiment group. The experiment group was treated with 654-2 injection and "Gan Xian Tui Huang Recipe" and the control group was treated with routine treatment. All the patients have high level of Nitrogen monoxide(NO), hyaluronic acid(HA > 400 ng/ml) and hepatic fibrosis with intractable jaundice. RESULTS: In experiment group, the serum total bilirubin(TB), globulin(GLB), HA and NO were significantly decreased to normal level; 40% of portal veins were narrowed, 50% of them were not changed; 30% of spleen were thinned, 40% of them were fixed. 1 year later, 20 patients were stable and 2 patients were recurrent in 22 patients of the experiment group; in 24 patients of the control group, 7 patients were stable, 10 patients had hypersplenia, 2 patients occurred hepatocarcinoma and 5 patients were recurrent. CONCLUSION: Effect of 654-2 injection and "Gan Xian Tui Huang Recipe" on hepatic fibrosis with intractable jaundice is significant.