title: Phase I study of chidamide (CS055/HBI-8000), a new histone deacetylase inhibitor, in patients with advanced solid tumors and lymphomas.
abstract: OBJECTIVE
  Chidamide (CS055/HBI-8000) is a new benzamide class of histone deacetylase inhibitor with marked anti-tumor activity. This study reports the phase I results.
  
  
  METHODS
  Patients with advanced solid tumors or lymphomas received oral doses of 5, 10, 17.5, 25, 32.5, or 50 mg chidamide either twice (BIW) or three times (TIW) per week for 4 consecutive weeks every 6 weeks. Safety, characteristics of pharmacokinetics (PK) and pharmacodynamics (PD), and preliminary efficacy were evaluated.
  
  
  RESULTS
  A total of 31 patients were enrolled. No DLTs were identified in the BIW cohorts up to 50 mg. DLTs were grade 3 diarrhea and vomiting in two patients in the TIW cohort at 50 mg, respectively. PK analysis revealed t(1/2) of 16.8-18.3 h, T(max) of 1-2 h in most cases, and a dose-related increase in C(max) and AUC. Significant induction of histone H3 acetylation in peripheral white blood cells was observed after a single dose of chidamide. Four patients with T-cell lymphomas and 1 patient with submandibular adenoid cystic carcinoma achieved a partial response.
  
  
  CONCLUSIONS
  Chidamide was generally well tolerated in patients with advanced solid tumors or lymphomas in the tested regimens. Favorable PK and PD profiles, as well as encouraging preliminary anti-tumor activity, were demonstrated.
authors.affiliation: Department of Medical Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, No. 17 Panjiayuan, Chaoyang District, Beijing, 100021, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Dong
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Ning
authors.forename: Pu-Yuan
authors.initials: PY
authors.lastname: Xing
authors.forename: Jia-Lian
authors.initials: JL
authors.lastname: Xu
authors.forename: Hai-Xiang
authors.initials: HX
authors.lastname: Cao
authors.forename: Gui-Fang
authors.initials: GF
authors.lastname: Dou
authors.forename: Zhi-Yun
authors.initials: ZY
authors.lastname: Meng
authors.forename: Yuan-Kai
authors.initials: YK
authors.lastname: Shi
authors.forename: Xian-Ping
authors.initials: XP
authors.lastname: Lu
authors.forename: Feng-Yi
authors.initials: FY
authors.lastname: Feng
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000631:Aminopyridines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001549:Benzamides / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use*; D006801:Humans; D008223:Lymphoma / Q000188:drug therapy*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*
chemical_list: D000631:Aminopyridines; D001549:Benzamides; D056572:Histone Deacetylase Inhibitors; C547816:N-(2-amino-5-fluorobenzyl)-4-(N-(pyridine-3-acrylyl)aminomethyl)benzamide