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

Abstract	Vandetanib (ZD6474; ZACTIMA, 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 < or = 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.
Authors	Roy S Herbst, John V Heymach, Michael S O'Reilly, Amir Onn, Anderson J Ryan
Journal	Expert opinion on investigational drugs (Expert Opin Investig Drugs) Vol. 16 Issue 2 Pg. 239-49 (Feb 2007) ISSN: 1744-7658 [Electronic] England
PMID	17243944 (Publication Type: Journal Article, Review)
Chemical References	Angiogenesis Inhibitors Antineoplastic Agents Piperidines Protein Kinase Inhibitors Quinazolines Receptor Protein-Tyrosine Kinases vandetanib
Topics	Administration, Oral Angiogenesis Inhibitors (administration & dosage, pharmacology) Animals Antineoplastic Agents (administration & dosage, pharmacology) Drug Delivery Systems (methods) Humans Neovascularization, Pathologic (drug therapy, metabolism) Piperidines (administration & dosage, chemistry, pharmacokinetics) Protein Kinase Inhibitors (administration & dosage, pharmacology) Quinazolines (administration & dosage, chemistry, pharmacokinetics) Receptor Protein-Tyrosine Kinases (antagonists & inhibitors, metabolism) Signal Transduction (drug effects, physiology)

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