Challenges associated with tyrosine kinase inhibitor therapy for metastatic thyroid cancer

Abstract

Tyrosine kinase inhibitors (TKIs) which target angiogenesis are promising treatments for patients with metastatic medullary and differentiated thyroid cancers. Sorafenib, sunitinib, and pazopanib are commercially available drugs which have been studied in these diseases. Vandetanib is the first drug approved in the United States for treatment of medullary thyroid cancer. These TKIs are used as chronic therapies, and therefore it is imperative to understand the adverse event profile in order to avoid excessive toxicity and maintain patients on therapy as long as it proves beneficial. Here we review common toxicities, management of these, and other challenging situations that arise when using TKIs in patients with thyroid cancer.

Figure 1

Transmission electron micrographs of endomyocardial biopsy from patient with systolic heart failure treated with a TKI. Section shows hypertrophy and interstitial edema with edematous mitochondria (open red arrow), with increased lipid droplets (solid red arrow) and dilatation of sarcotubular elements (yellow arrow). These findings are consistent with acute but reversible injury.

Figure 2

Patient with partial response in lymph nodes but progression in bone. CT scans before (a) and after (b) 6 months of therapy with a TKI. The patient had a partial response in mediastinal and hilar adenopathy but progression in bone with cortical destruction. The patient's bone lesions were irradiated, and he was restarted on the TKI. The patient continues on the TKI after 24 months and has no further evidence of progression.