0
selected
-
1.
Clinical efficacy of weight loss herbal intervention therapy and lifestyle modifications on obesity and its association with distinct gut microbiome: A randomized double-blind phase 2 study.
Cao, MZ, Wei, CH, Wen, MC, Song, Y, Srivastava, K, Yang, N, Shi, YM, Miao, M, Chung, D, Li, XM
Frontiers in endocrinology. 2023;:1054674
Abstract
GOALS To assess the efficacy and safety of Chinese Medicine Prescription "W-LHIT" in subjects with simple obesity, and to explore its potential mechanism of action. METHODS Thirty-seven patients aged 18 to 60 from Wei-En hospital (Weifang City, Shandong, China), participated in a double blinded, placebo-controlled study. Subjects were randomly divided into 2 groups, 18 in treatment and 19 in placebo group. The treatment group took the "W-LHIT" capsules for two months, while the control group received placebo capsules. Both groups accepted healthy lifestyle education materials. After a 2-month treatment, the placebo group transferred to open-label treatment after unblinding. RESULTS 72.22% participants in the treatment group lost more than 5% of their body weight, compared with 36.84% in the placebo group (p < 0.001). Body weight loss and body mass index reduction of the treatment group were also significantly higher than those of the placebo group (p < 0.05). These changes were accompanied by increased abundance of Akkermansia muciniphila and Enterococcus faecium, and decreased abundance of Proteobacteria in gut microbiota. Furthermore, the treatment group also showed improvement in obesity-related comorbidities such as hypertension and elevation of liver enzymes. No serious adverse reactions were found during the study period. Weight did not rebound at a follow-up visit 2 months after treatment. CONCLUSION W-LHIT significantly improved body weight and comorbid conditions without obvious adverse reaction or rebound weight gain. These effects were associated with increased abundance of probiotics in gut microbiota. W-LHIT may have a potential for treating obesity in conjunction with healthy lifestyle modifications.
-
2.
Efficacy and safety of weekly paclitaxel with or without ramucirumab as second-line therapy for the treatment of advanced gastric or gastroesophageal junction adenocarcinoma (RAINBOW-Asia): a randomised, multicentre, double-blind, phase 3 trial.
Xu, RH, Zhang, Y, Pan, H, Feng, J, Zhang, T, Liu, T, Qin, Y, Qin, S, Yin, X, Liu, B, et al
The lancet. Gastroenterology & hepatology. 2021;(12):1015-1024
Abstract
BACKGROUND In the global phase 3 RAINBOW study, ramucirumab plus paclitaxel significantly improved overall survival compared with placebo plus paclitaxel in patients with advanced gastric or gastro-oesophageal junction (GEJ) adenocarcinoma. RAINBOW-Asia, a bridging study with similar design to RAINBOW, aimed to evaluate the efficacy and safety of ramucirumab plus paclitaxel for advanced gastric or GEJ adenocarcinoma in Asian, predominantly Chinese, patients. METHODS RAINBOW-Asia was a randomised, double-blind, placebo-controlled, phase 3 trial done at 32 centres in China, Malaysia, the Philippines, and Thailand. Adult patients (≥18 years) with metastatic or locally advanced, unresectable gastric or GEJ adenocarcinoma who previously received fluoropyrimidine-platinum-based chemotherapy were randomly assigned with a centralised interactive web response system in a 2:1 ratio to receive ramucirumab 8 mg/kg or placebo intravenously on days 1 and 15 plus paclitaxel 80 mg/m2 intravenously on days 1, 8, and 15 of every 28-day cycle. Randomisation was stratified by Eastern Cooperative Oncology Group performance status and presence of peritoneal metastases. The co-primary endpoints were progression-free survival and overall survival. Efficacy analyses were done in the intention-to-treat population, and safety analysis included patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, NCT02898077, and has been completed. FINDINGS Between March 2, 2017, and June 30, 2020, 440 patients were randomly assigned to receive ramucirumab plus paclitaxel (n=294) or placebo plus paclitaxel (n=146). Median progression-free survival was 4·14 months (95% CI 3·71-4·30) in the ramucirumab plus paclitaxel group compared with 3·15 months (2·83-4·14) in the placebo plus paclitaxel group (hazard ratio [HR] 0·765, 95% CI 0·613-0·955, p=0·0184). Median overall survival was 8·71 months (95% CI 7·98-9·49) in the ramucirumab plus paclitaxel group and 7·92 months (6·31-9·10) in the placebo plus paclitaxel group (HR 0·963, 95% CI 0·771-1·203, p=0·7426). The most common grade 3 or worse treatment-emergent adverse events were decreased neutrophil count (159 [54%] of 293 patients in the ramucirumab plus paclitaxel group vs 56 [39%] of 145 in the placebo plus paclitaxel group), decreased white blood cell count (127 [43%] vs 42 [29%]), anaemia (46 [16%] vs 24 [17%]), hypertension (21 [7%] vs nine [6%]), and febrile neutropenia (18 [6%] vs one [<1%]). INTERPRETATION These findings, along with the results from RAINBOW, support the use of ramucirumab plus paclitaxel as second-line therapy in a predominantly Chinese population with advanced gastric or GEJ adenocarcinoma. FUNDING Eli Lilly and Company, USA. TRANSLATION For the Chinese translation of the abstract see Supplementary Materials section.
-
3.
Safety, Efficacy, and Pharmacokinetics of Almonertinib (HS-10296) in Pretreated Patients With EGFR-Mutated Advanced NSCLC: A Multicenter, Open-label, Phase 1 Trial.
Yang, JC, Camidge, DR, Yang, CT, Zhou, J, Guo, R, Chiu, CH, Chang, GC, Shiah, HS, Chen, Y, Wang, CC, et al
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer. 2020;(12):1907-1918
-
-
Free full text
-
Abstract
INTRODUCTION Almonertinib (HS-10296) is a novel, third-generation EGFR tyrosine kinase inhibitor (EGFR TKI) that targets both EGFR-sensitizing and T790M resistance mutations. This first-in-human trial aimed to evaluate the safety, efficacy, and pharmacokinetics of almonertinib in patients with locally advanced or metastatic EGFR mutation-positive NSCLC that had progressed after pevious EGFR TKI therapy. METHODS This phase 1, open-label, multicenter clinical trial (NCT0298110) included dose-escalation (55, 110, 220, and 260 mg) and dose-expansion cohorts (55, 110, and 220 mg) with once daily oral administration of almonertinib. In each expansion cohort, tumor biopsies were obtained for the determination of EGFR T790M status. The safety, tolerability, antitumor activity, and pharmacokinetics of almonertinib were evaluated. RESULTS A total of 120 patients (26 patients in the dose-escalation cohort and 94 patients in the dose-expansion cohort) were enrolled. The maximum tolerated dose was not defined in the dose-escalation phase; the 260 mg regimen was not further evaluated in the dose-expansion phase owing to safety concerns and saturation of exposure. The most common treatment-related grade greater than or equal to 3 adverse events were increased blood creatine phosphokinase (10%) and increased alanine aminotransferase (3%). Among 94 patients with the EGFR T790M mutation in the dose-expansion cohort, the investigator-assessed objective response rate and disease control rate were 52% (95% confidence interval [CI]: 42-63) and 92% (95% CI: 84-96), respectively. Median progression-free survival was 11.0 months (95% CI: 9.5-not reached) months. CONCLUSIONS Almonertinib is safe, tolerable and effective for patients with locally advanced or metastatic NSCLC harboring the EGFR T790M mutation who were pretreated with EGFR TKIs.
-
4.
Sorafenib and omacetaxine mepesuccinate as a safe and effective treatment for acute myeloid leukemia carrying internal tandem duplication of Fms-like tyrosine kinase 3.
Zhang, C, Lam, SSY, Leung, GMK, Tsui, SP, Yang, N, Ng, NKL, Ip, HW, Au, CH, Chan, TL, Ma, ESK, et al
Cancer. 2020;(2):344-353
-
-
Free full text
-
Abstract
BACKGROUND Omacetaxine mepesuccinate (OME) has antileukemic effects against acute myeloid leukemia (AML) carrying an internal tandem duplication of Fms-like tyrosine kinase 3 (FLT3-ITD). A phase 2 clinical trial was conducted to evaluate a combination treatment of sorafenib and omacetaxine mepesuccinate (SOME). METHODS Relapsed or refractory (R/R) or newly diagnosed patients were treated with sorafenib (200-400 mg twice daily) and OME (2 mg daily) for 7 (first course) or 5 days (second course onward) every 21 days until disease progression or allogeneic hematopoietic stem cell transplantation (HSCT). The primary endpoint was composite complete remission, which was defined as complete remission (CR) plus complete remission with incomplete hematologic recovery (CRi). Secondary endpoints were leukemia-free survival (LFS) and overall survival (OS). RESULTS Thirty-nine R/R patients and 5 newly diagnosed patients were recruited. Among the R/R patients, 28 achieved CR or CRi. Two patients showed partial remission, and 9 patients did not respond. Among the 5 newly diagnosed patients, 4 achieved CR, and 1 achieved CRi. The median LFS and OS were 5.6 and 10.9 months, respectively. Prior Fms-like tyrosine kinase 3 (FLT3) inhibitor exposure (P = .007), 2 or more inductions (P = .001), and coexisting IDH2 (P = .008) and RUNX1 mutations (P = .003) were associated with lower CR/CRi rates. HSCT consolidation and deep molecular responses (defined as an FLT3-ITD variant allelic frequency [VAF] ≤ 0.1% or a nucleophosmin 1 [NPM1] mutant VAF ≤ 0.01%) were associated with better OS and LFS. Prior FLT3 inhibitor exposure and 2 or more inductions were associated with inferior LFS. CONCLUSIONS SOME was safe and effective for R/R and newly diagnosed FLT3-ITD AML.
-
5.
Safety and tolerability of an antiasthma herbal Formula (ASHMI) in adult subjects with asthma: a randomized, double-blinded, placebo-controlled, dose-escalation phase I study.
Kelly-Pieper, K, Patil, SP, Busse, P, Yang, N, Sampson, H, Li, XM, Wisnivesky, JP, Kattan, M
Journal of alternative and complementary medicine (New York, N.Y.). 2009;(7):735-43
-
-
Free full text
-
Abstract
BACKGROUND Complementary and alternative medicines are increasingly used for the treatment of asthma in Western countries. A novel three-herb antiasthma herbal medicine intervention (ASHMI; Sino-Lion Pharmaceutical Company; Shan Dong China) was demonstrated to be effective and safe in a murine model of asthma and in a preliminary clinical study in China. OBJECTIVE The objective of this study was to evaluate the safety and tolerability of ASHMI in adult subjects with allergic asthma. DESIGN Randomized, double-blind, placebo-controlled, dose escalation, phase I trial aimed at developing a botanical drug under the United States Food and Drug Administration Investigational New Drug title. INTERVENTIONS Subjects received one of three doses of ASHMI or placebo: 600 mg (2 capsules); 1200 mg (4 capsules); or 1800 mg (6 capsules) twice daily for 1 week. Four (4) ASHMI and 2 placebo subjects were treated at each dose level. Subjects continued to use their conventional asthma medications for the duration of the study. OUTCOME MEASURES Vital signs, physical examination, laboratory data, and electrocardiogram data were monitored throughout the study to assess occurrence of adverse events (AEs). Immunomodulatory studies were performed to evaluate the effect of ASHMI on cytokine, chemokine, and growth factor levels. RESULTS Twenty (20) nonsmoking, allergic subjects with asthma were included in the study. Eight (8) subjects (4 ASHMI and 4 placebo) reported mild gastrointestinal symptoms. No grade 3 AEs were observed during the study period. Vital signs, electrocardiogram findings, and laboratory results obtained at pre- and post-treatment visits remained within normal range. No abnormal immunologic alterations were detected. CONCLUSION In this phase I study, ASHMI appeared to be safe and well tolerated by subjects with asthma. These findings allowed initiation of a larger phase II study to assess the efficacy of ASHMI.
-
6.
[Effect of astraglus injection on serum apoptosis relevant factors in patients with chronic heart failure].
Zhang, JG, Yang, N, He, H
Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine. 2005;(5):400-3
Abstract
OBJECTIVE To investigate the effect of Astragalus injection (AGI) on serum apoptosis related factors such as soluble Fas (sFas), soluble Fas ligand (sFasL) and tumor necrosis factor alpha (TNF-alpha) in patients with chronic heart failure (CHF). METHODS Eighty-four patients with CHF of NYHA II-IV grade were randomly divided into two groups, the treated group (42 patients) treated with AGI and the control group (42 patients) treated with routine treatment. The level of serum sFas, sFasL, and TNF-alpha were measured with ELISA before and after treatment. At the same time, patients' heart function were graded according to the NYHA classification and their indices of left ventricular function were determined. RESULTS Patients' NYHA grade was improved in both groups after treatment (P < 0.05 or P < 0.01), and it was better in the treated group than that in the control group (P < 0.05). Moreover, in the treated group, the left ventricular end-systolic volume (LVESV) and left ventricular end-diastolic volume (LVEDV) decreased, the left ventricular ejection fraction (LVEF) increased, which was significantly different than that before treatment (P < 0.05) respectively; level of serum apoptosis related factors sFas, sFas L and TNF-alpha were significantly decreased after treatment, showing significant difference as compared with those before treatment or with those in the control group after treatment (P < 0.05 or P < 0.01). While all indices had no obvious change in the control group. CONCLUSION AGI may be regarded as an effective remedy for treatment of CHF owing to its effects in decreasing the level of serum apoptosis related factors in patients with CHF.