Systemic
chemotherapies for advanced or metastatic
thyroid carcinomas have been of only limited effectiveness. For patients with differentiated or
medullary carcinomas unresponsive to conventional treatments, novel
therapies are needed to improve disease outcomes. Multiple novel
therapies primarily targeting angiogenesis have entered clinical trials for metastatic
thyroid carcinoma. Partial response rates up to 30% have been reported in single-agent studies, but prolonged disease stabilization is more commonly observed. The most successful agents target the
vascular endothelial growth factor receptors, with potential targets including the mutant
kinases associated with papillary and medullary
oncogenesis. Two drugs approved for other
malignancies,
sorafenib and
sunitinib, have had promising preliminary results reported, and are being used selectively for patients who do not qualify for clinical trials. At least one randomized, placebo-controlled phase III trial has been successfully completed, showing improved progression-free survival in patients with advanced or metastatic medullary
thyroid carcinoma treated with
vandetanib. Randomized trials for other agents are currently underway. Treatment for patients with metastatic or advanced
thyroid carcinoma now emphasizes clinical trial opportunities for novel agents with considerable promise. Alternative options now exist for use of
tyrosine kinase inhibitors that are well tolerated and may prove worthy of regulatory approval for this disease.