A pharmacokinetic and safety study of a fixed oral dose of enzastaurin HCl in native Chinese patients with refractory solid tumors and lymphoma
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Xueying Li1,*, Xiaojie Fang1,*, Su Li2, Weijing Zhang3, Nong Yang4, Yimin Cui5, He Huang1, Ruiqing Cai1, Xiaoting Lin1, Xiaohong Fu1, Huangming Hong1, Tongyu Lin1
1Department 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
2Department 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
3Department of Lymphoma, The 307th Hospital of Chinese People’s Liberation Army, Beijing, China
4Department of Medical Oncology, Hunan Cancer Hospital, Changsha, China
5Department of Pharmacy, Peking University First Hospital, Beijing, China
*These authors contributed equally to this work
Tongyu Lin, e-mail: email@example.com
Keywords: enzastaurin, pharmacokinetics, safety, solid tumors, lymphoma
Received: November 07, 2015 Accepted: January 29, 2016 Published: March 03, 2016
Purpose: 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 t1/2, Cav, ss, and AUCτ, 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.
Trial Registration: ClinicalTrials.gov: NCT01432951
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