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Safety, pharmacokinetics, and antitumor properties of anlotinib, an oral multi-target tyrosine kinase inhibitor, in patients with advanced refractory solid tumors

文献类型：期刊论文

作者Sun, Yongkun1,2; Niu, Wei3; Du, Feng4; Du, Chunxia1,2; Li, Shuting1,2; Wang, Jinwan1,2; Li, Li3; Wang, Fengqing3; Hao, Yu5; Li, Chuan3
刊名JOURNAL OF HEMATOLOGY & ONCOLOGY
出版日期2016-10-04
卷号9
关键词Anlotinib Anti-angiogenesis Phase I study Advanced refractory solid tumors Pharmacokinetics Safety
ISSN号1756-8722
DOI10.1186/s13045-016-0332-8
文献子类Article
英文摘要Background: Anlotinib is a novel multi-target tyrosine kinase inhibitor that is designed to primarily inhibit VEGFR2/3, FGFR1-4, PDGFR alpha/beta, c-Kit, and Ret. We aimed to evaluate the safety, pharmacokinetics, and antitumor activity of anlotinib in patients with advanced refractory solid tumors. Methods: Anlotinib (5-16 mg) was orally administered in patients with solid tumor once a day on two schedules: (1) four consecutive weeks (4/0) or (2) 2-week on/1-week off (2/1). Pharmacokinetic sampling was performed in all patients. Twenty-one patients were further enrolled in an expanded cohort study on the recommended dose and schedule. Preliminary tumor response was also assessed. Results: On the 4/0 schedule, dose-limiting toxicity (DLT) was grade 3 hypertension at 10 mg. On the 2/1 schedule, DLT was grade 3 hypertension and grade 3 fatigue at 16 mg. Pharmacokinetic assessment indicated that anlotinib had long elimination half-lives and significant accumulation during multiple oral doses. The 2/1 schedule was selected, with 12 mg once daily as the maximum tolerated dose for the expanding study. Twenty of the 21 patients (with colon adenocarcinoma, non-small cell lung cancer, renal clear cell cancer, medullary thyroid carcinoma, and soft tissue sarcoma) were assessable for antitumor activity of anlotinib: 3 patients had partial response, 14 patients had stable disease including 12 tumor burden shrinkage, and 3 had disease progression. The main serious adverse effects were hypertension, triglyceride elevation, hand-foot skin reaction, and lipase elevation. Conclusions: At the dose of 12 mg once daily at the 2/1 schedule, anlotinib displayed manageable toxicity, long circulation, and broad-spectrum antitumor potential, justifying the conduct of further studies.
WOS关键词RENAL-CELL CARCINOMA ; EXPANDED-ACCESS ; GASTRIC-CANCER ; SORAFENIB ; EFFICACY ; AMPLIFICATION ; HALLMARKS ; BREAST ; LUNG
资助项目Jiangsu Chia-tai Tianqing Pharmaceutical Co., Ltd.[00000000]
WOS研究方向Oncology ; Hematology
语种英语
WOS记录号WOS:000385894700001
出版者BMC
源URL[http://119.78.100.183/handle/2S10ELR8/275866]  
专题上海药物代谢研究中心
中科院受体结构与功能重点实验室
新药研究国家重点实验室
科研与新药推进处
通讯作者Li, Chuan; Chi, Yihebali
作者单位1.Chinese Acad Med Sci, Canc Hosp, Dept Med Oncol, Beijing 100021, Peoples R China;
2.PUMC, Beijing 100021, Peoples R China;
3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China;
4.Peking Univ, Canc Hosp & Inst, Dept Med, VIPII Gastrointestinal Canc Div, Beijing 100142, Peoples R China;
5.Nanjing Med Univ, Sch Publ Hlth, Nanjing, Jiangsu, Peoples R China
推荐引用方式
GB/T 7714		 Sun, Yongkun,Niu, Wei,Du, Feng,et al. Safety, pharmacokinetics, and antitumor properties of anlotinib, an oral multi-target tyrosine kinase inhibitor, in patients with advanced refractory solid tumors[J]. JOURNAL OF HEMATOLOGY & ONCOLOGY,2016,9.
APA Sun, Yongkun.,Niu, Wei.,Du, Feng.,Du, Chunxia.,Li, Shuting.,...&Chi, Yihebali.(2016).Safety, pharmacokinetics, and antitumor properties of anlotinib, an oral multi-target tyrosine kinase inhibitor, in patients with advanced refractory solid tumors.JOURNAL OF HEMATOLOGY & ONCOLOGY,9.
MLA Sun, Yongkun,et al."Safety, pharmacokinetics, and antitumor properties of anlotinib, an oral multi-target tyrosine kinase inhibitor, in patients with advanced refractory solid tumors".JOURNAL OF HEMATOLOGY & ONCOLOGY 9(2016).

入库方式： OAI收割

来源：上海药物研究所

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