title: A pharmacokinetic and safety study of a fixed oral dose of enzastaurin HCl in native Chinese patients with refractory solid tumors and lymphoma.
abstract: OBJECTIVE
  This study was conducted to assess the pharmacokinetics and safety of enzastaurin in native Chinese patients with refractory solid tumors and lymphoma.
  
  
  METHODS
  Eligible patients received 500 mg of enzastaurin orally once daily. The pharmacokinetics of enzastaurin and its metabolites were assessed on days 14 to 18. Patients were allowed to continue receiving the agent in a safety extension phase until disease progression or presentation with unacceptable toxicity.
  
  
  RESULTS
  Twenty-five patients received at least 1 dose of enzastaurin, and twenty-one patients completed the pharmacokinetic phase. Fifteen patients entered the safety extension phase. Except for transient, asymptomatic grade 3 QT interval prolongation in one patient who had baseline grade 2 QT prolongation, other adverse events were of grade 1 to 2. The t(1/2), C(av, ss), and AUC(τ,ss) for enzastaurin and its primary active metabolite LSN326020 were 14 and 42 h, 1,210 and 907 nmol/L, and 29,100 and 21,800 nmol•h/L, respectively. One patient with relapsed diffuse large B-cell lymphoma achieved a partial response that lasted for 8.1 months.
  
  
  CONCLUSIONS
  The pharmacokinetics of enzastaurin in Chinese cancer patients were consistent with those observed in previous studies abroad. Enzastaurin 500 mg daily was well tolerated by Chinese patients. We recommend 500 mg daily as the phase II dose in this population. Its efficacy in lymphoma deserves further investigation.
  
  
  BACKGROUND
  ClinicalTrials.gov: NCT01432951.
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.
authors.forename: Xueying
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Fang
authors.affiliation: Department of Clinical Trials Research Center, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.
authors.forename: Su
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Lymphoma, The 307th Hospital of Chinese People's Liberation Army, Beijing, China.
authors.forename: Weijing
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Medical Oncology, Hunan Cancer Hospital, Changsha, China.
authors.forename: Nong
authors.initials: N
authors.lastname: Yang
authors.affiliation: Department of Pharmacy, Peking University First Hospital, Beijing, China.
authors.forename: Yimin
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.
authors.forename: He
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.
authors.forename: Ruiqing
authors.initials: R
authors.lastname: Cai
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.
authors.forename: Xiaoting
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Fu
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.
authors.forename: Huangming
authors.initials: H
authors.lastname: Hong
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.
authors.forename: Tongyu
authors.initials: T
authors.lastname: Lin
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism*
chemical_list: D007211:Indoles; C504878:enzastaurin
keywords: enzastaurin; lymphoma; pharmacokinetics; safety; solid tumors