Vandetanib (ZD6474): an orally available receptor tyrosine kinase inhibitor that selectively targets pathways critical for tumor growth and angiogenesis

被引：125

作者：

Herbst, Roy S. ^{[1
]}

Heymach, John V. ^{[1
]}

O'Reilly, Michael S. ^{[1
]}

Onn, Amir ^{[1
]}

Ryan, Anderson J. ^{[1
]}

机构：

[1] Univ Texas, MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Unit 432, Houston, TX 77030 USA

来源：

EXPERT OPINION ON INVESTIGATIONAL DRUGS | 2007年 / 16卷 / 02期

关键词：

angiogenesis inhibitor; medullary thyroid cancer; non-small cell tung cancer; tyrosine kinase inhibitor; vandetanib; ZD6474;

D O I：

10.1517/13543784.16.2.239

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Vandetanib (ZD6474; ZACTIMA(TM), AstraZeneca) is a once-daily, orally available agent with potential for use in a number of solid tumor types. Vandetanib targets key signaling pathways in cancer by inhibiting VEGFR-dependent tumor angiogenesis, and EGFR- and RET-dependent tumor cell proliferation and survival. Phase I studies showed vandetanib to be generally well tolerated at doses of <= 300 mg/day, with a pharmacokinetic profile that supports once-daily oral administration. Phase II evaluation of vandetanib in patients with advanced refractory NSCLC has demonstrated improvements in progression-free survival both as monotherapy (versus gefitinib) and in combination with docetaxel (versus docetaxel alone). These positive outcomes have led to the initiation of Phase III trials of vandetanib in advanced NSCLC. Clinical development is also ongoing in other tumor types and encouraging evidence of antitumor activity has been reported in patients with metastatic hereditary medullary thyroid cancer.

引用

页码：239 / 249

页数：11