Vandetanib is an orally available receptor tyrosine kinase (RTK) inhibitor, which blocks both the vascular endothelial growth factor (VEGF) RTK and the Epidermal Growth Factor (EGF) RTK. Blockade of the VEGF receptors limits the growth of new blood vessels, which are vital to supporting the growth of tumors. Without sufficient blood supply, tumor cells become starved for nutrients, slowing or halting growth.
Vandetanib is specifically indicated for the treatment of symptomatic or progressive medullary thyroid cancer in patients with unresectable locally advanced or metastatic disease.
Vandetanib is supplied as a tablet for oral administration. The recommended daily dose is 300 mg of vandetanib taken orally, with or wothout food. Vandetanib treatment should be continued until patients are no longer benefiting from treatment or an unacceptable toxicity occurs.
Vandetanib tablets should not be crushed. If vandetanib tablets cannot be taken whole, the tablets can be dispersed in a glass containing 2 ounces of non-carbonated water and stirred until the tablet is dispersed. The dispersion should be swallowed immediately. To ensure the full dose is received, any residues in the glass should be mixed again with an additional 4 ounces of non-carbonated water and swallowed.
The FDA approval of Vandetanib was based on a double-blind, placebo-controlled study in 331 subjects with unresectable locally advanced or metastatic medullary thyroid cancer. The subjects received vandetanib 300 mg or placebo. The primary objective was demonstration of improvement in progression-free survival (PFS) with vandetanib compared to placebo. Other endpoints included evaluation of overall survival and overall objective response rate (ORR). The result of the PFS analysis, based on the central review RECIST assessment, showed a statistically significant improvement in PFS for subjects randomized to vandetanib (p<0.0001). Analyses in the subgroups of subjects who were symptomatic or had progressed within six months prior to their enrollment showed similar PFS results. At the time of the primary analysis of PFS, 15% of the subjects had died and there was no significant difference in overall survival between the two treatment groups. The overall objective response rate (ORR) for subjects randomized to vandetanib was 44% compared to 1% for subjects randomized to placebo. All objective responses were partial responses.
Adverse events associated with the use of Vandetanib may include, but are not limited to, the following:
Vandetanib is a kinase inhibitor. In vitro studies have shown that vandetanib inhibits the activity of tyrosine kinases including members of the epidermal growth factor receptor (EGFR) family, vascular endothelial cell growth factor (VEGF) receptors, rearranged during transfection (RET), protein tyrosine kinase 6 (BRK), TIE2, members of the EPH receptors kinase family, and members of the Src family of tyrosine kinases. Vandetanib inhibits endothelial cell migration, proliferation, survival and new blood vessel formation in in vitro models of angiogenesis. Vandetanib inhibits EGFR-dependent cell survival in vitro. In addition, vandetanib inhibits epidermal growth factor (EGF)-stimulated receptor tyrosine kinase phosphorylation in tumor cells and endothelial cells and VEGF-stimulated tyrosine kinase phosphorylation in endothelial cells. In vivo vandetanib administration reduced tumor cell-induced angiogenesis, tumor vessel permeability, and inhibited tumor growth and metastasis in mouse models of cancer.
Robinson BG, Paz-Ares L, Krebs A, Vasselli J, Haddad R Vandetanib (100 mg) in patients with locally advanced or metastatic hereditary medullary thyroid cancer. The Journal of clinical endocrinology and metabolism 2010 Jun;95(6):2664-71
Wells SA Jr, Gosnell JE, Gagel RF, Moley J, Pfister D, Sosa JA, Skinner M, Krebs A, Vasselli J, Schlumberger M Vandetanib for the treatment of patients with locally advanced or metastatic hereditary medullary thyroid cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2010 Feb 10;28(5):767-72
Sathornsumetee S, Rich JN Vandetanib, a novel multitargeted kinase inhibitor, in cancer therapy. Drugs Today 2006 Oct;42(10):657-70
For additional information regarding Vandetanib or thyroid cancer, please visit the AstraZeneca web page.