Article thumbnail

Vandetanib (ZD6474) in the Treatment of Medullary Thyroid Cancer

By Hari Deshpande, Sanziana Roman, Jaykumar Thumar and Julie Ann Sosa

Abstract

Vandetanib (ZD6474) is an orally bioavailable small molecule tyrosine kinase inhibitor of multiple growth factor receptors, including RET (Rearrange during transfection), vascular endothelial growth factor receptor-2 (VEGFR-2) and epidermal growth factor receptor (EGFR). The activity against RET and VEGF made it a good choice in the treatment of medullary thyroid cancer (MTC). As there is considerable cross talk between growth factor pathways, dual inhibition with such agents has become an attractive strategy, in the treatment of many malignancies with encouraging Phase II clinical trial data to date. Vandetanib was tested in two Phase II trials in the treatment of patients with medullary thyroid cancer at doses of 100 mg and 300 mg daily respectively. The encouraging results of these 2 trials led to a randomized phase II trial comparing this medication to placebo using a crossover design. More than 300 patients were included in this study, which ultimately showed a significant improvement in progression-free survival in patients taking vandetanib. Based on these results, the Oncology Drug Advisory Committee (ODAC) of the Food and Drug Administration (FDA) recommended that vandetanib be approved for the treatment of patients with unresectable locally advanced or metastatic medullary thyroid cancer

Topics: Review
Publisher: Libertas Academica
OAI identifier: oai:pubmedcentral.nih.gov:3153121
Provided by: PubMed Central

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.

Suggested articles

Citations

  1. A phase I dose-escalation study of ZD6474 in Japanese patients with solid, malignant tumors.
  2. (2008). A phase I study of XL184, a MET, VEGFR2, and RET kinase inhibitor, administered orally to patients (pts) with advanced malignancies including a subgroup of patients with medullary thyroid cancer (MTC).
  3. (2008). A phase II open-label study of vandetanib in patients with locally advanced or metastatic hereditary medullary thyroid cancer. J Clin Oncol.
  4. Activation of a novel human transforming gene, ret, by DNA rearrangement.
  5. Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome.
  6. (2008). Axitinib is an active treatment for all histologic subtypes of advanced thyroid cancer: results from a phase II study. J Clin Oncol.
  7. Axitinib: The evidence of its potential in the treatment of advanced thyroid cancer. Core Evid.
  8. Capecitabine therapy for refractory metastatic thyroid carcinoma: a case series.
  9. Chemotherapy of thyroid carcinoma.
  10. (2010). Chemotherapy with paclitaxel and gemcitabine in progressive medullary and thyroid carcinoma of the follicular epithelium. Horm Metab Res.
  11. (2005). Clinical evaluation of ZD6474, an orally active inhibitor of VEGF and EGF receptor signaling, in patients with solid, malignant tumors. Ann Oncol.
  12. Familial amyloid-producing medullary thyroid carcinoma and pheochromocytoma. A distinct genetic entity.
  13. Familial thyroid cancer.
  14. Guidelines for diagnosis and therapy of MEN type 1 and type 2.
  15. Increased expression of vascular endothelial growth factor and its receptors, VEGFR-1 and VEGFR-2, in medullary thyroid carcinoma.
  16. (2010). Long-term results in a cohort of medullary thyroid cancer (MTC) patients (pts) in a phase I study of XL184 (BMS 907351), an oral inhibitor of MET, VEGFR2, and RET.
  17. Medullary (solid) carcinoma of the thyroid; a clinicopathologic entity.
  18. Medullary thyroid carcinoma.
  19. (2008). Novel chemotherapy options for advanced thyroid tumors: small molecules offer great hope. Curr Opin Oncol.
  20. Phase II clinical trial of sorafenib in metastatic medullary thyroid cancer.
  21. (2010). Phase II study of daily sunitinib in FDG-PET-positive, iodinerefractory differentiated thyroid cancer and metastatic medullary carcinoma of the thyroid with functional imaging correlation. Clin Cancer Res.
  22. Phase II study of safety and efficacy of motesanib in patients with progressive or symptomatic, advanced or metastatic medullary thyroid cancer.
  23. Prognosis of medullary thyroid carcinoma: demographic, clinical, and pathologic predictors of survival in 1252 cases.
  24. RET proto-oncogene in the development of human cancer.
  25. (1968). Study of a kindred with pheochromocytoma, medullary thyroid carcinoma, hyperparathyroidism and Cushing’s disease: multiple endocrine neoplasia, type 2. Medicine (Baltimore).
  26. (2007). Technology insight: gene therapy and its potential role in the treatment of medullary thyroid carcinoma. Nat Clin Pract Endocrinol Metab.
  27. The association of pheochromocytoma with carcinoma of the thyroid gland.
  28. The biology of VEGF and its receptors.
  29. (2008). The genetic basis of hereditary medullary thyroid cancer: clinical implications for the surgeon, with a particular emphasis on the role of prophylactic thyroidectomy. Endocr Relat Cancer.
  30. The relationship between specific RET proto-oncogene mutations and disease phenotype in multiple endocrine neoplasia type 2. International RET mutation consortium analysis.
  31. (2008). Thyroid tumors, in Cancer: Principles and Practice of Oncology,
  32. (2007). Vandetanib (ZD6474): an orally available receptor tyrosine kinase inhibitor that selectively targets pathways critical for tumor growth and angiogenesis. Expert Opin Investig Drugs.
  33. Vandetanib for the treatment of patients with locally advanced or metastatic hereditary medullary thyroid cancer.
  34. (2002). ZD6474 inhibits vascular endothelial growth factor signaling, angiogenesis, and tumor growth following oral administration. Cancer Res.
  35. (2002). ZD6474, an orally available inhibitor of KDR tyrosine kinase activity, efficiently blocks oncogenic RET kinases. Cancer Res.