Targeted therapy for endocrine cancer: the medullary thyroid carcinoma paradigm.

OBJECTIVE: To provide an overview of a new approach for treatment of medullary thyroid carcinoma (MTC) and other endocrine tumors.

METHODS: This review compiles recent information from the medical literature and scientific meetings focused on the use of tyrosine kinase inhibitors (TKIs) for the treatment of MTC and other endocrine tumors.

RESULTS: The elucidation during the past 2 decades of multiple genetic abnormalities in endocrine tumors has provided specific targets for therapy. The identification of activating mutations of the RET tyrosine kinase receptor in both hereditary and sporadic MTC makes this malignant disease an excellent model for examination of the effect of a group of small organic molecule TKIs for treatment of metastatic MTC. Clinical trials with several TKIs targeting RET and other tyrosine kinase receptors have shown positive results with generally tolerable toxicity. Approximately one-third to one-half of patients with MTC have a reduction in tumor size of 0% to 50%, with the longest treatment duration of approximately 4 years. The most common treatment-related toxic effects are cutaneous effects, nausea, and diarrhea. Cardiovascular toxicity, such as hypertension, prolongation of the corrected QT interval, or heart failure, is uncommon but may be serious.

CONCLUSION: Despite promising initial results, these studies are in their early stages, and none of these therapies is currently approved by the US Food and Drug Administration for treatment in the United States. These studies highlight the potential for targeting endocrine cancer signaling pathways and provide a paradigm for treatment of endocrine cancer.