Management of advanced stage medullary thyroid carcinoma. Therapy with tyrosine kinase inhibitors

Medullary thyroid carcinoma (MTC) is a slowly growing tumor of neuroendocrine origin with a good prognosis and patient quality of life, which can be cured by surgery. Patients with persistent postoperative disease, slightly elevated calcitonin (Ct) level, low tumor burden and stable disease are often asymptomatic. A small subset of patients shows aggressive tumor growth. In patients with a significant tumor burden and advanced or progressive metastatic MTC, therapy with tyrosine kinase inhibitors (TKI) is now available. The clinical impact of the novel TKI therapy in the setting of long-term follow-up management of patients with advanced metastatic MTC was evaluated. Selection criteria for local and systemic treatment based on recent trials and guidelines are discussed. Patients with rapidly growing MTC, as determined by sequential imaging studies using response evaluation criteria in solid tumors (RECIST), and by documented shortened doubling times of serum Ct and carcinoembryonic antigen (CEA) levels, should be considered for systemic therapy. In this setting, TKIs such as vandetanib and cabozantinib, appear to be the most effective treatment modality. They achieve significant improvement of progression-free survival in patients with progressive metastatic MTC. However, TKIs have a significant toxicity requiring dose reduction or even interruption of treatment. Treatment with TKIs represents an important new therapeutic option for patients with progressive metastatic MTC; however, there are several unresolved questions, such as continuous or intermittent therapy, combination therapy, second line treatment after progress under TKI treatment and initiation of treatment at an earlier stage?.