Objective: The recurrence or progression under endocrine therapy in hormone receptor-positive(HR+)advanced breast cancer(ABC) remained a critical clinical challenge.Chidamide is an oral subtype-selective histone deace...Objective: The recurrence or progression under endocrine therapy in hormone receptor-positive(HR+)advanced breast cancer(ABC) remained a critical clinical challenge.Chidamide is an oral subtype-selective histone deacetylase(HDAC) inhibitor with multiple functions in tumor growth inhibition and microenvironment modulation via epigenetic reprogramming.The purpose of this study was to evaluate the safety,pharmacokinetics(PK),and preliminary efficacy of chidamide in combination with exemestane in HR+ ABC patients.Methods: Eligible patients were postmenopausal women with HR+ ABC recurrent or progressed to at least one endocrine therapy.Blood samples were obtained in the run-in period and the first day of combination treatment for PK analysis.In combination treatment,patients were given exemestane 25mg daily and chidamide 30mg twice a week(BIW) until progression of disease or intolerable toxicities.A treatment cycle was defined as 4 weeks.Safety,PK parameters,and preliminary efficacy were evaluated.Results: A total of 20 patients were enrolled between July and December,2015.The median number of treatments cycle was 5.2(20.8 weeks) with 2 patients still on treatment at the data cut-off date of October,2017.The treatment-related adverse events(AE) ≥ grade 3 in more than 2 patients were neutropenia(35%),thrombocytopenia(30%),and leucopenia(20%).The plasma exposure of exemestane was consistent in the presence or absence of chidamide.A slight increase in chidamide exposure was noted in the presence of exemestane,probably due to the inter-and intra-patient variations.The best response in 16 evaluable patients was assessed by Response Evaluation Criteria in Solid Tumors(RECIST),including 4 patients with partial response,10 patients with stable disease.The median progression-free survival(PFS) was 7.6 months.Conclusions: The combination of chidamide with exemestane was generally well tolerated with promising preliminary efficacy in HR+ ABC patients.The overall results from this study encourage further pivotal trial in this patient population.展开更多
Objective:Chidamide is an oral histone deacetylase subtype-selective inhibitor approved for relapsed or refractory peripheral T-cell lymphoma(PTCL).This phase 1 b study evaluated the safety,pharmacokinetics,and prelim...Objective:Chidamide is an oral histone deacetylase subtype-selective inhibitor approved for relapsed or refractory peripheral T-cell lymphoma(PTCL).This phase 1 b study evaluated the safety,pharmacokinetics,and preliminary efficacy of chidamide in combination with cyclophosphamide,doxorubicin,vincristine and prednisone(CHOP)for treatment-na?ve PTCL patients.Methods:This study was an open-label,multicenter trial composed of dose escalation and dose expansion.Patients received CHOP for six 21-d cycles and chidamide on d 1,4,8 and 11 in each cycle.Four dose levels of chidamide(20,25,30 and 35 mg)were evaluated.The primary objective was to evaluate the safety and tolerability of the combination regimen.Results:A total of 30 patients were evaluated in this study:15 in the dose-escalation part and 15 in the doseexpansion part.In the dose-escalation study,three patients were enrolled in the 35 mg chidamide cohort.One had dose-limiting toxicity with grade 3 vascular access complications,and one had grade 2 neutropenia with a sustained temperature>38°C.Dose escalation was stopped at this chidamide dose level.The most common(≥10%)grade 3 or 4 adverse events(AEs)were leukopenia(90.0%),neutropenia(83.3%),vomiting(13.3%),thrombocytopenia(10.0%)and febrile neutropenia(10.0%).No significant changes in chidamide pharmacokinetic properties were observed before and after combination treatment.The objective response rate for the 28 patients evaluable for preliminary efficacy was 89.3%(25/28),with 16(57.1%)achieving complete response or unconfirmed complete response.The estimated median progression-free survival was 14.0 months.In summary,we chose chidamide 30 mg as the recommended dose for phase 2.Conclusions:The addition of chidamide to standard CHOP chemotherapy was tolerable with promising preliminary efficacy in previously untreated PTCL patients,which supports further clinical studies with this combination regimen for the frontline treatment of PTCL.展开更多
By employing zinc acetate and sodium hydroxide as raw materials, ultrafine ZnO powders with different morphologies were successfully synthesized through hydrothermal method. The influences of the reaction temperature,...By employing zinc acetate and sodium hydroxide as raw materials, ultrafine ZnO powders with different morphologies were successfully synthesized through hydrothermal method. The influences of the reaction temperature, the OH-/Zn2＋ mol ratio and the reaction time on the morphologies of the ZnO powders were discussed. The reaction conditions were obtained, under which the ZnO of flower-like particles, micro-rods and flake particles was synthesized, respectively. The crystal structures and morphologies of those ZnO particles were characterized by X-ray diffraction （XRD） and scanning electron microscopy （SEM）. The ZnO with flower-like structures was composed of lots of micro-rods with hexagon morphology. The XRD patterns indicated that the ZnO powders were hexagonal wurtzite structures with high purity. Finally, the growth mechanism of the ZnO particles was discussed.展开更多
基金partly supported by grants from the Chinese National Major Project for New Drug Innovation(No.2015ZX09101005)the Shenzhen municipal science and technology project(No.JCYJ20120618162903087 and No.JSGG20140515161400837)
文摘Objective: The recurrence or progression under endocrine therapy in hormone receptor-positive(HR+)advanced breast cancer(ABC) remained a critical clinical challenge.Chidamide is an oral subtype-selective histone deacetylase(HDAC) inhibitor with multiple functions in tumor growth inhibition and microenvironment modulation via epigenetic reprogramming.The purpose of this study was to evaluate the safety,pharmacokinetics(PK),and preliminary efficacy of chidamide in combination with exemestane in HR+ ABC patients.Methods: Eligible patients were postmenopausal women with HR+ ABC recurrent or progressed to at least one endocrine therapy.Blood samples were obtained in the run-in period and the first day of combination treatment for PK analysis.In combination treatment,patients were given exemestane 25mg daily and chidamide 30mg twice a week(BIW) until progression of disease or intolerable toxicities.A treatment cycle was defined as 4 weeks.Safety,PK parameters,and preliminary efficacy were evaluated.Results: A total of 20 patients were enrolled between July and December,2015.The median number of treatments cycle was 5.2(20.8 weeks) with 2 patients still on treatment at the data cut-off date of October,2017.The treatment-related adverse events(AE) ≥ grade 3 in more than 2 patients were neutropenia(35%),thrombocytopenia(30%),and leucopenia(20%).The plasma exposure of exemestane was consistent in the presence or absence of chidamide.A slight increase in chidamide exposure was noted in the presence of exemestane,probably due to the inter-and intra-patient variations.The best response in 16 evaluable patients was assessed by Response Evaluation Criteria in Solid Tumors(RECIST),including 4 patients with partial response,10 patients with stable disease.The median progression-free survival(PFS) was 7.6 months.Conclusions: The combination of chidamide with exemestane was generally well tolerated with promising preliminary efficacy in HR+ ABC patients.The overall results from this study encourage further pivotal trial in this patient population.
基金supported by the sponsor Shenzhen Chipscreen Biosciences Co.,LTD.by grants from the China National Major Project for New Drug Innovation(No.2017ZX09304015)the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(CIFMS)(No.2016-I2M-1-001)。
文摘Objective:Chidamide is an oral histone deacetylase subtype-selective inhibitor approved for relapsed or refractory peripheral T-cell lymphoma(PTCL).This phase 1 b study evaluated the safety,pharmacokinetics,and preliminary efficacy of chidamide in combination with cyclophosphamide,doxorubicin,vincristine and prednisone(CHOP)for treatment-na?ve PTCL patients.Methods:This study was an open-label,multicenter trial composed of dose escalation and dose expansion.Patients received CHOP for six 21-d cycles and chidamide on d 1,4,8 and 11 in each cycle.Four dose levels of chidamide(20,25,30 and 35 mg)were evaluated.The primary objective was to evaluate the safety and tolerability of the combination regimen.Results:A total of 30 patients were evaluated in this study:15 in the dose-escalation part and 15 in the doseexpansion part.In the dose-escalation study,three patients were enrolled in the 35 mg chidamide cohort.One had dose-limiting toxicity with grade 3 vascular access complications,and one had grade 2 neutropenia with a sustained temperature>38°C.Dose escalation was stopped at this chidamide dose level.The most common(≥10%)grade 3 or 4 adverse events(AEs)were leukopenia(90.0%),neutropenia(83.3%),vomiting(13.3%),thrombocytopenia(10.0%)and febrile neutropenia(10.0%).No significant changes in chidamide pharmacokinetic properties were observed before and after combination treatment.The objective response rate for the 28 patients evaluable for preliminary efficacy was 89.3%(25/28),with 16(57.1%)achieving complete response or unconfirmed complete response.The estimated median progression-free survival was 14.0 months.In summary,we chose chidamide 30 mg as the recommended dose for phase 2.Conclusions:The addition of chidamide to standard CHOP chemotherapy was tolerable with promising preliminary efficacy in previously untreated PTCL patients,which supports further clinical studies with this combination regimen for the frontline treatment of PTCL.
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)。
基金the Chinese National and Provincial Major Project for New Drug Innovation(National:2008ZX09101-002,2013ZX09401301Provincial:2011A080501010)Shenzhen Municipal Major Project(2010-1746)。
基金supported by the National Natural Science Foundation of China (No. 51204054)the Fundamental Research Funds for the Central Universities, China (No.N110402012)
文摘By employing zinc acetate and sodium hydroxide as raw materials, ultrafine ZnO powders with different morphologies were successfully synthesized through hydrothermal method. The influences of the reaction temperature, the OH-/Zn2＋ mol ratio and the reaction time on the morphologies of the ZnO powders were discussed. The reaction conditions were obtained, under which the ZnO of flower-like particles, micro-rods and flake particles was synthesized, respectively. The crystal structures and morphologies of those ZnO particles were characterized by X-ray diffraction （XRD） and scanning electron microscopy （SEM）. The ZnO with flower-like structures was composed of lots of micro-rods with hexagon morphology. The XRD patterns indicated that the ZnO powders were hexagonal wurtzite structures with high purity. Finally, the growth mechanism of the ZnO particles was discussed.
