Safety and pharmacokinetics of novel selective vascular endothelial growth factor receptor-2 inhibitor YN968D1 in patients with advanced malignancies
文献类型：期刊论文
| 作者 | Li, Jin1,3; Zhao, Xinmin1,3; Chen, Lei1,3; Guo, Haiyi1,3; Lv, Fangfang1,3; Jia, Ka1,3; Yv, Ke2; Wang, Fengqing2; Li, Chuan2; Qian, Jun1,3 |
| 刊名 | BMC CANCER
 |
| 出版日期 | 2010-10-05 |
| 卷号 | 10 |
| ISSN号 | 1471-2407 |
| DOI | 10.1186/1471-2407-10-529 |
| 文献子类 | Article |
| 英文摘要 | Background: YN968D1 (Apatinib) selectively inhibits phosphorylation of VEGFR-2 and tumor angiogenesis in mice model. The study was conducted to determine the maximum tolerated dose (MTD), safety profile, pharmacokinetic variables, and antitumor activity in advanced solid malignancies. Methods: This dose-escalation study was conducted according to the Chinese State Food and Drug Administration (SFDA) recommendations in patients with advanced solid tumors to determine the MTD for orally administered apatinib. Doses of continuously administered apatinib were escalated from 250 mg. Treatment continued after dose-escalation phase until withdrawal of consent, intolerable toxicities, disease progression or death. Results: Forty-six patients were enrolled. Hypertension and hand-foot syndrome were the two dose-limiting toxicities noted at dose level of 1000 mg. MTD was determined to be 850 mg once daily. Pharmacokinetic analysis showed early absorption with a half-life of 9 hours. The mean half-life was constant over all dose groups. Steady-state conditions analysis suggested no accumulation during 56 days of once-daily administration. The most frequently observed drug-related adverse events were hypertension (69.5%, 29 grade 1-2 and 3 grade 3-4), proteinuria (47.8%, 16 grade 1-2 and 6 grade 3-4), and hand-foot syndrome (45.6%, 15 grade 1-2 and 6 grade 3-4). Among the thirty-seven evaluable patients, PR was noted in seven patients (18.9%), SD 24 (64.9%), with a disease control rate of 83.8% at 8 weeks. Conclusions: The recommended dose of 750 mg once daily was well tolerated. Encouraging antitumor activity across a broad range of malignancies warrants further evaluation in selected populations. |
| WOS关键词 | METASTATIC COLORECTAL-CANCER ; REFRACTORY SOLID TUMORS ; ANGIOGENESIS ; HYPERTENSION ; SUNITINIB |
| WOS研究方向 | Oncology |
| 语种 | 英语 |
| WOS记录号 | WOS:000284113600001 |
| 出版者 | BIOMED CENTRAL LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278752]  |
| 专题 | 上海药物代谢研究中心 科研与新药推进处 |
| 通讯作者 | Li, Jin |
| 作者单位 | 1.Fudan Univ, Shanghai Canc Ctr, Dept Med Oncol, Shanghai 200032, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 3.Fudan Univ, Shanghai Med Coll, Dept Oncol, Shanghai 200032, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Li, Jin,Zhao, Xinmin,Chen, Lei,et al. Safety and pharmacokinetics of novel selective vascular endothelial growth factor receptor-2 inhibitor YN968D1 in patients with advanced malignancies[J]. BMC CANCER,2010,10. |
| APA | Li, Jin.,Zhao, Xinmin.,Chen, Lei.,Guo, Haiyi.,Lv, Fangfang.,...&Zuo, Yunxia.(2010).Safety and pharmacokinetics of novel selective vascular endothelial growth factor receptor-2 inhibitor YN968D1 in patients with advanced malignancies.BMC CANCER,10. |
| MLA | Li, Jin,et al."Safety and pharmacokinetics of novel selective vascular endothelial growth factor receptor-2 inhibitor YN968D1 in patients with advanced malignancies".BMC CANCER 10(2010). |
入库方式： OAI收割
来源：上海药物研究所
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