Medullary thyroid cancer medical therapy
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Medullary thyroid cancer Microchapters |
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Differentiating Medullary thyroid cancer from other Diseases |
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ammu Susheela, M.D. [2]
Overview
Medical Therapy
Protein kinase inhibitors
Clinical trials of protein kinase inhibitors,[1] which block the abnormal kinase proteins involved in the development and growth of medullary cancer cells, showed clear evidence of response in 10-30% of patients. In the majority of responders there has been less than a 30% decrease in tumor mass, yet the responses have been durable; responses have been stable for periods exceeding 3 years. The major side effects of this class of drug include hypertension, nausea, diarrhea, some cardiac electrical abnormalities, and thrombotic or bleeding episodes.
Vandetanib, trade name Caprelsa, was the first drug (April 2011) to be approved by US Food and Drug Administration (FDA) for treatment of late-stage (metastatic) medullary thyroid cancer in adult patients who are ineligible for surgery.[2]
Cabozantinib, trade name Cometriq, was granted marketing approval (November 2012) by the U.S. FDA for this indication.[3] Cabozantinib which is a potent inhibitor of RET, MET and VEGF was evaluated in a double-blind placebo controlled trial. It was shown to improve overall survival by 5 months for the treated cohort vs. placebo, which was not statistically significant. However, cabozantinib was particularly effective in patients with the RET M918T mutation, extending overall survival by roughly 2 years, doubling survival vs. untreated patient (4 years vs. 2 year). Treatment with cabozantinib did require many dose reduction to mitigate side effects. It has been suggested that the trial dose of 140 mg was excessive, particularly in lower body mass patients. Ongoing trials have been scheduled to identify more optimal dosing regimes. Activity has been observed, in practice at doeses of 1.2 mg/kg.
Reference
- ↑ "American Thyroid Association - Thyroid Clinical Trials". Retrieved 2007-12-21.
- ↑ "FDA approves new treatment for rare form of thyroid cancer". Retrieved 7 April 2011.
- ↑ "FDA approves Cometriq to treat rare type of thyroid cancer". Retrieved 29 November 2012.