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New directions in the systemic treatment of metastatic thyroid cancer.

Medical oncologists have traditionally had little to offer patients with metastatic radioactive iodine-resistant thyroid cancer. The 3-year survival rate of patients with differentiated thyroid cancer is less than 50%, with little response obtained from standard cytotoxic chemotherapies. In recent years, however, huge advances have been made in understanding the molecular pathways and cellular pathogenesis of this disease. This knowledge has in turn led to the development of a range of targeted therapies, some specific to thyroid cancer genetic alterations such as the RET/PTC translocation, and others that exploit general malignant properties such as angiogenesis. This review highlights novel targeted agents for the treatment of differentiated and medullary thyroid cancers being studied at this time, and the results of recently published trials. We propose that such patients should be managed, whenever possible, within a clinical trial, in order to access the most promising new drugs for thyroid cancer. In cases where trials are unavailable, we recommend off-label use of the currently available oral multikinase inhibitors such as sorafenib and sunitinib rather than traditional chemotherapies.