Vandetanib (ZD6474): an orally available receptor tyrosine kinase inhibitor that selectively targets pathways critical for tumor growth and angiogenesis.
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.
Herbst
Roy S
RS
The University of Texas MD Anderson Cancer Center, Department of Thoracic/Head and Neck Medical Oncology, 1515 Holcombe Boulevard, Unit 432, Houston, TX 77030-4009, USA. rherbst@mdanderson.org
Heymach
John V
JV
O'Reilly
Michael S
MS
Onn
Amir
A
Ryan
Anderson J
AJ
D000284:Administration, Oral; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods; D006801:Humans; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000378:metabolism; D010880:Piperidines / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D011799:Quinazolines / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D020794:Receptor Protein-Tyrosine Kinases; C452423:vandetanib