Exploratory clinical study of chidamide,an oral subtype-selective histone deacetylase inhibitor,in combination with exemestane in hormone receptor-positive advanced breast cancer  

作　　者：Qingyuan Zhang Tao Wang Cuizhi Geng Yue Zhang Jinwen Zhang Zhiqiang Ning Zefei Jiang 

机构地区：[1]Department of Medical Oncology,Harbin Medical University Cancer Hospital,Harbin 150081,China [2]Department of Breast Cancer,the 307th hospital of Chinese People's Liberation Army,Beijing 100071,China [3]The Fourth Hospital of Hebei Medical University,Shijiazhuang 050011,China [4]Shenzhen Chipscreen Biosciences,Shenzhen 518057,China

出　　处：《Chinese Journal of Cancer Research》2018年第6期605-612,共8页中国癌症研究（英文版）

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)

摘　　要：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 pObjective: 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 p

关 键 词：Advanced breast cancer hormone receptor-positive CHIDAMIDE EXEMESTANE 

分 类 号：R[医药卫生]