TYROSINE KINASE INHIBITORS IN ADVANCED THYROID CANCER

In the last decades significant progresses have been made in the field of cancer therapy, among all the so-called targeted therapy. Tyrosine kinase inhibitors (TKIs) are example of these new strategy and they have been used in many solid and hematologic tumors. TKIs are small molecules that inhibit tyrosine kinases, enzymes responsible for the activation of signal transduction cascades, through phosphorylation of various proteins. TKIs have been used in advanced thyroid cancer refractory to conventional treatment. So far, in MTC patients TKIs (motesanib, sunitinib, vandetanib, sorafenib, cabozantinib, axitinib) have determined an overall objective response (stable disease and partial response) ranging 45-92% while in DTC patients between 49-82%. From 2005 to 2010 we participated in 5 international randomized trials, double-blind or in a single arm, using 5 different TKIs. We enrolled 21 patients with MTC patients and 10 with DTC. Among patients with MTC, taking the drug and not the placebo, we observed 38% of stable disease and 22% of partial response. In DTC patients we had nearly 50% of objective response. In general, limitations using TKIs are represented by adverse reactions, principally dermatological, and resistance. In conclusion, TKIs seem to be a promising class of drugs to treat advanced thyroid cancer, refractory to conventional treatment with quite manageable side effects.