Phase I study of the safety, pharmacokinetics and antitumor activity of famitinib

doi:10.1007/s00280-013-2282-y

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	Phase I study of the safety, pharmacokinetics and antitumor activity of famitinib
	Zhou, Aiping 1; Zhang, Wen 1; Chang, Chunxiao 1; Chen, Xiaoyan2 ; Zhong, Dafang2 ; Qin, Qiong 1; Lou, Donghua 3; Jiang, Haoyuan 4; Wang, Jinwan 1
刊名	CANCER CHEMOTHERAPY AND PHARMACOLOGY
	2013-11
卷号	72 期号:5 页码:1043-1053
关键词	Famitinib Phase I trial Safety Pharmacokinetics Antitumor activity
ISSN号	0344-5704
DOI	10.1007/s00280-013-2282-y
文献子类	Article
英文摘要	To evaluate the safety, tolerability, pharmacokinetics and antitumor activities of famitinib (famitinib l-malate), a novel oral multitargeting tyrosine kinase inhibitor that acts against vascular endothelial growth factor receptor-2, platelet-derived growth factor receptor, stem cell factor receptor (c-kit), FMS-like tyrosine kinase-3 receptor and protooncogene tyrosine kinase receptor in patients with advanced solid cancer. Patients received once daily oral famitinib. Doses were increased from 4 to 8, 13, 20, 27, 24, 25 and eventually 30 mg. Each cycle was defined as 28 days. The pharmacokinetic profile and various biomarkers were evaluated during the first cycle. Antitumor efficacy was evaluated every 8 weeks. Fifty-four patients were evaluable for safety and efficacy. Dose-limiting toxicities were observed in 2 of 3 patients at 30 mg. The dose-limiting toxicities observed in the first cycle of famitinib treatment included hypertension, hand-foot skin reaction and diarrhea. Grade 3 hypertriglyceridemia/hypercholesterolemia and proteinuria were notable side effects in the subsequent treatment cycles. Other common side effects included bone marrow suppression, oral mucositis, fatigue, pain, elevated transaminase or bilirubin, peripheral sensory disturbance and hypothyroidism, most of which were mild to moderate in severity. Pharmacokinetic studies revealed no significant accumulation of famitinib or its major metabolite, M3. The half-lives of famitinib and M3 were approximately 28.7-33.8 and 41.3-47.7 h, respectively. Food demonstrated a minimal effect on the pharmacokinetics of famitinib. Eight partial responses were determined, including 6 cases of renal cell carcinoma, 1 case of gastrointestinal stromal tumor (GIST) and 1 case of alveolar soft part sarcoma. Fourteen patients demonstrated stable disease with various degrees of tumor shrinkage. Famitinib is generally well tolerated. Famitinib demonstrates a wide spectrum of antitumor activities, which warrants further study in renal cell carcinoma, GIST, hepatocellular carcinoma and soft tissue sarcoma. The recommended dose for future phase II clinical trials is 25 mg.
资助项目	Jiangsu Hengrui Medicine Co. Ltd.[00000000]
WOS关键词	RENAL-CELL CARCINOMA ; TYROSINE KINASE INHIBITOR ; SUNITINIB TREATMENT ; INTERFERON-ALPHA ; CANCER ; SORAFENIB ; EFFICACY ; TEMSIROLIMUS ; OUTCOMES ; SU11248
WOS研究方向	Oncology ; Pharmacology & Pharmacy
语种	英语
出版者	SPRINGER
WOS记录号	WOS:000326100400011
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/277405]
专题	上海药物代谢研究中心
通讯作者	Wang, Jinwan
作者单位	1.Chinese Acad Med Sci, Peking Union Med Coll, Canc Hosp & Inst, Dept Med Oncol, Beijing 100730, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Drug Metab & Pharmacokinet Res, Shanghai 200031, Peoples R China; 3.Nanjing Med Univ, Dept Epidemiol & Biostat, Nanjing, Jiangsu, Peoples R China; 4.Jiangsu Hengrui Med Co Ltd, Dept Clin Dev, Lianyungang, Peoples R China
推荐引用方式 GB/T 7714	Zhou, Aiping,Zhang, Wen,Chang, Chunxiao,et al. Phase I study of the safety, pharmacokinetics and antitumor activity of famitinib[J]. CANCER CHEMOTHERAPY AND PHARMACOLOGY,2013,72(5):1043-1053.
APA	Zhou, Aiping.,Zhang, Wen.,Chang, Chunxiao.,Chen, Xiaoyan.,Zhong, Dafang.,...&Wang, Jinwan.(2013).Phase I study of the safety, pharmacokinetics and antitumor activity of famitinib.CANCER CHEMOTHERAPY AND PHARMACOLOGY,72(5),1043-1053.
MLA	Zhou, Aiping,et al."Phase I study of the safety, pharmacokinetics and antitumor activity of famitinib".CANCER CHEMOTHERAPY AND PHARMACOLOGY 72.5(2013):1043-1053.