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Background: Treatment of advanced medullary thyroid carcinoma (MTC) was recently improved with the approval of vandetanib and cabozantinib. However, there is still a need to explore sequential therapy with more than one tyrosine kinase inhibitor (TKI) and to explore alternative therapies when vandetanib and cabozantinib are not available. This study reports the authors' experience with sorafenib as a treatment for advanced MTC. Methods: This is a retrospective longitudinal study of 13 patients with progressive metastatic MTC treated with sorafenib 400 mg twice daily between December 2011 and January 2015. The primary endpoints were to evaluate response and progression-free survival (PFS) in patients treated with sorafenib outside a clinical trial. The secondary endpoint was an assessment of the toxicity profile. One patient was excluded because of a serious allergic skin rash one week after starting sorafenib. Results: The analysis included 12 patients with metastatic MTC (median age 48 years), 10 with sporadic and 2 with hereditary disease. The median duration of treatment was 11 months, and the median follow-up was 15.5 months. At data cutoff, 2/12 (16%) patients were still on treatment for 16 and 34 months. According to Response Evaluation Criteria in Solid Tumors analysis, 10 (83.3%) patients showed stable disease, and two (16.6%) had progression of disease; no partial response was observed. The median PFS was nine months. However, three patients with extensive and rapidly progressive disease died within three months of sorafenib treatment. The median PFS excluding these three patients was 12 months. Adverse events (AE) occurred in nine (75%) patients. The main AEs were skin toxicity, weight loss, and fatigue. Five (41.6%) patients needed dose reduction, and one patient discontinued treatment because of toxicity. Conclusions: Treatment with sorafenib in progressive metastatic MTC is well tolerated and resulted in disease control and durable clinical benefit in 75% of patients. Sorafenib treatment could be considered when vandetanib and cabozantinib are not available or after failing these drugs. [ABSTRACT FROM AUTHOR]

Background: The treatment of advanced medullary thyroid carcinoma (MTC) has significantly evolved over the past decade. The discovery of genetic abnormalities in MTC led to the development of targeted therapies such as vandetanib and cabozantinib. Other kinase inhibitors (KI), such as Sorafenib, have been investigated in this setting and are an alternative therapeutic option. The lack of specificity of these KIs to a single target may result in additional, unexpected effects. In this report, we describe a patient with metastatic MTC and ectopic ACTH syndrome in whom treatment with Sorafenib resulted in complete resolution of hypercortisolism. Summary: A 45 year-old male with progressive metastatic MTC presented with clinical manifestations suspicious for Cushing's syndrome. Investigation revealed ACTH-dependent hypercortisolism suggestive of ectopic ACTH syndrome. Treatment with Sorafenib 400 mg twice a day was initiated resulting in a rapid and significant reduction of cortisol and ACTH levels associated with dramatic clinical improvement. The rapid and effective control of hypercortisolism in the absence of a significant tumor reduction raises the question whether sorafenib may have a direct effect on ACTH or cortisol hypersecretion. Conclusions: This report suggests a previously unknown potential effect of sorafenib on the pituitary-adrenal axis. Further studies will be necessary to investigate the role of sorafenib in other cases of ACTH excess and to understand the mechanisms by which it alters steroid synthesis, action or secretion. [ABSTRACT FROM AUTHOR]