Objective: To evaluate the therapeutic effect of the fludarabine and cytarabine (FA) regimen on acute myeloid leukemia (AML) at different phases during treatment. Methods: A total of 185 patients with AML were divided...Objective: To evaluate the therapeutic effect of the fludarabine and cytarabine (FA) regimen on acute myeloid leukemia (AML) at different phases during treatment. Methods: A total of 185 patients with AML were divided into 4 groups based on the outcome of previous treatments. Patients in Group 1 had no remission after the first course of induction chemotherapy (n = 55). Patients in Group 2 had no remission after no less than two courses of induction chemotherapy (n = 41). Patients in Group 3 had early relapse (n = 40). Patients in Group 4 had late relapse (n = 49). Patients in groups 2, 3 and 4 had refractory AML or AML with relapse. We assessed the efficacy and toxicity of FA combination chemotherapy in each of these 4 groups. Results: The complete remission (CR) rates of Groups 1, 2, 3 and 4 were 74.5% (41/55), 45.9% (19/41), 17.5% (7/40) and 38.8% (19/49), respectively. The CR rate was higher in Group 1 than in the other 3 groups (34.6%, 45/130) (P = 0.000). A significant correlation was found between CR rate and the number of chemotherapeutic courses (P = 0.023). The main adverse reactions included bone marrow suppression and secondary infection. Conclusion: FA regimen is a good choice for patients with AML, especially those who have failed to achieve CR after the first course of induction chemotherapy.展开更多
Chiglitazar(Carfloglitazar)is a novel non-thiazolidinedione(TZD)structured peroxisome proliferatoractivated receptor(PPAR)pan-agonist that has shown promising effects on glycemic control and lipid regulation in patien...Chiglitazar(Carfloglitazar)is a novel non-thiazolidinedione(TZD)structured peroxisome proliferatoractivated receptor(PPAR)pan-agonist that has shown promising effects on glycemic control and lipid regulation in patients with type 2 diabetes in previous clinical studies.This randomized phase 3 trial aimed to compare the efficacy and safety of chiglitazar with placebo in patients with type 2 diabetes with insufficient glycemic control by strict diet and exercise alone.Eligible patients were randomly assigned to receive chiglitazar 32 mg(n=167),chiglitazar 48 mg(n=166),or placebo(n=202)once daily.The primary endpoint was the change in glycosylated hemoglobin A_(1c)(HbA_(1c))at week 24 with superiority of chiglitazar over placebo.The results showed that both chiglitazar 32 and 48 mg resulted in significant and clinically meaningful reductions in HbA_(1c),and placebo-adjusted estimated treatment differences at week 24 for chiglitazar 32 and 48 mg were-0.87%(95%confidential interval(CI):-1.10 to-0.65;P<0.0001)and-1.05%(95%CI:-1.29 to-0.81;P<0.0001),respectively.Secondary efficacy parameters including glycemic control,insulin sensitivity and triglyceride reduction were also significantly improved in the chiglitazar groups.The overall frequency of adverse events and study discontinuation attributable to adverse events were similar among the groups.Low incidences of mild edema and body weight gain were reported in the chiglitazar dose groups.The results from this phase 3 trial demonstrated that the PPAR pan-agonist chiglitazar possesses an overall good efficacy and safety profile in patients with type 2 diabetes inadequately controlled with lifestyle interventions,thereby providing adequate supporting evidence for using this PPAR pan-agonist as a treatment option for type 2 diabetes.展开更多
Chiglitazar(Carfloglitazar)is a novel peroxisome proliferator-activated receptor(PPAR)pan-agonist that has shown promising effects on glycemic control and lipid regulation in patients with type 2 diabetes.In this rand...Chiglitazar(Carfloglitazar)is a novel peroxisome proliferator-activated receptor(PPAR)pan-agonist that has shown promising effects on glycemic control and lipid regulation in patients with type 2 diabetes.In this randomized phase 3 trial,we compared the efficacy and safety of chiglitazar with sitagliptin in patients with type 2 diabetes who had insufficient glycemic control despite a strict diet and exercise regimen.Eligible patients were randomized(1:1:1)to receive chiglitazar 32 mg(n=245),chiglitazar 48 mg(n=246),or sitagliptin 100 mg(n=248)once daily for 24 weeks.The primary endpoint was the change in glycosylated hemoglobin A_(1C)(HbA_(1c))from baseline at week 24 with the non-inferiority of chiglitazar over sitagliptin.Both chiglitazar and sitagliptin significantly reduced HbA1c at week 24 with values of-1.40%,-1.47%,and-1.39%for chiglitazar 32 mg,chiglitazar 48 mg,and sitagliptin 100 mg,respectively.Chiglitazar 32 and 48 mg were both non-inferior to sitagliptin 100 mg,with mean differences of-0.04%(95%confidential interval(Cl)-0.22 to 0.15)and-0.08%(95%Cl-0.27 to 0.10),respectively.Compared with sitagliptin,greater reduction in fasting and 2-h postprandial plasma glucose and fasting insulin was observed with chiglitazar.Overall adverse event rates were similar between the groups.A small increase in mild edema in the chiglitazar 48 mg group and slight weight gain in both chiglitazar groups were reported.The overall results demonstrated that chiglitazar possesses good efficacy and safety profile in patients with type 2 diabetes inadequately controlled with lifestyle interventions,thereby providing adequate supporting evidence for using this PPAR pan-agonist as a treatment option for type 2 diabetes.展开更多
Although advances have been made, chemotherapy for chronic, multifactorial diseases such as cancers, Alzheimer's disease, cardiovascular diseases and diabetes is far from satisfactory. Agents with different mechan...Although advances have been made, chemotherapy for chronic, multifactorial diseases such as cancers, Alzheimer's disease, cardiovascular diseases and diabetes is far from satisfactory. Agents with different mechanisms of action are required. The botanic compound berberine(BBR) has been used as an over-the-counter antibacterial for diarrhea in China for many decades. Recent clinical studies have shown that BBR may be therapeutic in various types of chronic diseases. This review addresses BBR's molecular mechanisms of action and clinical efficacy and safety in patients with type 2 diabetes, hyperlipidemia, heart diseases, cancers and inflammation. One of the advantages of BBR is its multiple-target effects in each of these diseases. The therapeutic efficacy of BBR may reflect a synergistic regulation of these targets, resulting in a comprehensive effect against these various chronic disorders. The safety of BBR may be due to its harmonious distribution into those targets. Although the single-target concept is still the principle for drug discovery and research, this review emphasizes the concept of a multiple target strategy, which may be an important approach toward the successful treatment of multifactorial chronic diseases.展开更多
基金Supported by a grant from the Planned Science and Technology Project of Guangzhou (No. 2006Z3-E0401)
文摘Objective: To evaluate the therapeutic effect of the fludarabine and cytarabine (FA) regimen on acute myeloid leukemia (AML) at different phases during treatment. Methods: A total of 185 patients with AML were divided into 4 groups based on the outcome of previous treatments. Patients in Group 1 had no remission after the first course of induction chemotherapy (n = 55). Patients in Group 2 had no remission after no less than two courses of induction chemotherapy (n = 41). Patients in Group 3 had early relapse (n = 40). Patients in Group 4 had late relapse (n = 49). Patients in groups 2, 3 and 4 had refractory AML or AML with relapse. We assessed the efficacy and toxicity of FA combination chemotherapy in each of these 4 groups. Results: The complete remission (CR) rates of Groups 1, 2, 3 and 4 were 74.5% (41/55), 45.9% (19/41), 17.5% (7/40) and 38.8% (19/49), respectively. The CR rate was higher in Group 1 than in the other 3 groups (34.6%, 45/130) (P = 0.000). A significant correlation was found between CR rate and the number of chemotherapeutic courses (P = 0.023). The main adverse reactions included bone marrow suppression and secondary infection. Conclusion: FA regimen is a good choice for patients with AML, especially those who have failed to achieve CR after the first course of induction chemotherapy.
基金grants from Chinese National and Provincial Major Project for New Drug Innovation(National:2008ZX09101-002 and 2013ZX09401301Provincial:2011A080501010)Shenzhen Municipal Major Project(2010-1746)。
文摘Chiglitazar(Carfloglitazar)is a novel non-thiazolidinedione(TZD)structured peroxisome proliferatoractivated receptor(PPAR)pan-agonist that has shown promising effects on glycemic control and lipid regulation in patients with type 2 diabetes in previous clinical studies.This randomized phase 3 trial aimed to compare the efficacy and safety of chiglitazar with placebo in patients with type 2 diabetes with insufficient glycemic control by strict diet and exercise alone.Eligible patients were randomly assigned to receive chiglitazar 32 mg(n=167),chiglitazar 48 mg(n=166),or placebo(n=202)once daily.The primary endpoint was the change in glycosylated hemoglobin A_(1c)(HbA_(1c))at week 24 with superiority of chiglitazar over placebo.The results showed that both chiglitazar 32 and 48 mg resulted in significant and clinically meaningful reductions in HbA_(1c),and placebo-adjusted estimated treatment differences at week 24 for chiglitazar 32 and 48 mg were-0.87%(95%confidential interval(CI):-1.10 to-0.65;P<0.0001)and-1.05%(95%CI:-1.29 to-0.81;P<0.0001),respectively.Secondary efficacy parameters including glycemic control,insulin sensitivity and triglyceride reduction were also significantly improved in the chiglitazar groups.The overall frequency of adverse events and study discontinuation attributable to adverse events were similar among the groups.Low incidences of mild edema and body weight gain were reported in the chiglitazar dose groups.The results from this phase 3 trial demonstrated that the PPAR pan-agonist chiglitazar possesses an overall good efficacy and safety profile in patients with type 2 diabetes inadequately controlled with lifestyle interventions,thereby providing adequate supporting evidence for using this PPAR pan-agonist as a treatment option for type 2 diabetes.
基金the Chinese National and Provincial Major Project for New Drug Innovation(National:2008ZX09101-002,2013ZX09401301Provincial:2011A080501010)Shenzhen Municipal Major Project(2010-1746)。
文摘Chiglitazar(Carfloglitazar)is a novel peroxisome proliferator-activated receptor(PPAR)pan-agonist that has shown promising effects on glycemic control and lipid regulation in patients with type 2 diabetes.In this randomized phase 3 trial,we compared the efficacy and safety of chiglitazar with sitagliptin in patients with type 2 diabetes who had insufficient glycemic control despite a strict diet and exercise regimen.Eligible patients were randomized(1:1:1)to receive chiglitazar 32 mg(n=245),chiglitazar 48 mg(n=246),or sitagliptin 100 mg(n=248)once daily for 24 weeks.The primary endpoint was the change in glycosylated hemoglobin A_(1C)(HbA_(1c))from baseline at week 24 with the non-inferiority of chiglitazar over sitagliptin.Both chiglitazar and sitagliptin significantly reduced HbA1c at week 24 with values of-1.40%,-1.47%,and-1.39%for chiglitazar 32 mg,chiglitazar 48 mg,and sitagliptin 100 mg,respectively.Chiglitazar 32 and 48 mg were both non-inferior to sitagliptin 100 mg,with mean differences of-0.04%(95%confidential interval(Cl)-0.22 to 0.15)and-0.08%(95%Cl-0.27 to 0.10),respectively.Compared with sitagliptin,greater reduction in fasting and 2-h postprandial plasma glucose and fasting insulin was observed with chiglitazar.Overall adverse event rates were similar between the groups.A small increase in mild edema in the chiglitazar 48 mg group and slight weight gain in both chiglitazar groups were reported.The overall results demonstrated that chiglitazar possesses good efficacy and safety profile in patients with type 2 diabetes inadequately controlled with lifestyle interventions,thereby providing adequate supporting evidence for using this PPAR pan-agonist as a treatment option for type 2 diabetes.
基金supported by the National Mega-Project for Drug Research&Development,China(to Jiang Jian Dong)
文摘Although advances have been made, chemotherapy for chronic, multifactorial diseases such as cancers, Alzheimer's disease, cardiovascular diseases and diabetes is far from satisfactory. Agents with different mechanisms of action are required. The botanic compound berberine(BBR) has been used as an over-the-counter antibacterial for diarrhea in China for many decades. Recent clinical studies have shown that BBR may be therapeutic in various types of chronic diseases. This review addresses BBR's molecular mechanisms of action and clinical efficacy and safety in patients with type 2 diabetes, hyperlipidemia, heart diseases, cancers and inflammation. One of the advantages of BBR is its multiple-target effects in each of these diseases. The therapeutic efficacy of BBR may reflect a synergistic regulation of these targets, resulting in a comprehensive effect against these various chronic disorders. The safety of BBR may be due to its harmonious distribution into those targets. Although the single-target concept is still the principle for drug discovery and research, this review emphasizes the concept of a multiple target strategy, which may be an important approach toward the successful treatment of multifactorial chronic diseases.