Vandetanib for the Treatment of Metastatic Medullary Thyroid Cancer

Abstract

Medullary thyroid cancer (MTC) represents an aggressive form of thyroid malignancy. Some may occur spontaneously or can be associated with Multiple Endocrine Neoplasia syndromes, or Familial Medullary Thyroid Cancer syndrome. In these patients, the protooncogene RET (rearranged during transfection) is mutated. In patients who have unresectable or metastatic disease, the long term prognosis is poor. New treatments for this disease have focused on the use of targeted agents that inhibit the receptor tyrosine kinase of RET. One of these treatments, Vandetanib (Caprelsa, Astra Zeneca), recently has received approval from the Food and Drug Administration for the treatment of patients with progressive locally advanced and/or metastatic disease. This review highlights the studies that led to the drug’s approval, and discusses on the potential financial costs of treatment and side effects of this therapy. The main clinical studies evaluating Vandetanib for the treatment of other solid tumors will also be reviewed.

Metabolism and Pharmacokinetics of Novel Selective Vascular Endothelial Growth Factor Receptor-2 Inhibitor Apatinib in Humans

“…The VEGFR-family proteins consist of three members: VEGFR-1 (Flt-1), VEGFR-2 (KDR/Flk-1), and VEGFR-3 (Flt-4), among which VEGFR-2 is thought to be principally responsible for angiogenesis in malignancies (Glade-Bender et al, 2003). Small-molecule VEGFR inhibitors are widely used for the treatment of metastatic renal cell carcinoma, gastrointestinal stromal tumors, hepatocellular carcinoma (Ivy et al, 2009), soft tissue sarcoma (Gennigens and Jerusalem, 2012), and medullary thyroid cancer (Degrauwe et al, 2012) and in the development of a number of other oncology indications, including colorectal cancer, non-small-cell lung cancer, pancreatic cancer, ovarian cancer, and breast cancer (Ivy et al, 2009).…”

Vandetanib‐associated alopecia areata in a patient with metastatic medullary thyroid cancer

“…These gain-of-function mutations are observed in medullary thyroid cancer, as well as in familial medullary thyroid cancer, multiple neuroendocrine neoplasia (MEN, types 2A and 2B), and pheochromocytoma. 1 Vascular endothelial growth factor receptor and EGF receptor have also been found to contribute to the pathogenesis of medullary thyroid cancer. They stimulate angiogenesis, leading to cell growth and proliferation.…”

“…It interacts with the rearranged during transfection (RET) receptor, the epidermal growth factor (EGF) receptor, and the vascular endothelial growth factor (VEGF) receptor. 1 Vandetanib has also been shown to prolong progression-free survival in patients with non-small cell lung cancer and other solid tumors such as medullary thyroid cancer. 2 RET gene mutations are believed to be the main oncogenic cause of medullary thyroid cancer.…”

Isolation and structure elucidation of the main UV-A photoproducts of vandetanib

“…Vandetanib shows an acceptable safety and tolerability profile with a majority of the adverse events manageable with supportive therapy or dose reduction [7]. As many other multikinase inhibitors [8], skin is one of the main affected organs for its side effects: in fact, at least in part, the cutaneous toxicity can be explained by the fact that the signaling pathways and/or receptors are physiologically expressed in the skin.…”