Sorafenib: Rays of Hope in Thyroid Cancer

Background: Sorafenib (BAY 43-9006) is an inhibitor of multiple-receptor tyrosine kinases involved in tumor growth and angiogenesis, which can be advantageously administered orally. Initially used as monotherapy in advanced renal cell carcinoma, sorafenib was proven to increase progression-free survival while enhancing disease control. Clinical trials on sorafenib are at present ongoing for the treatment of various malignancies, including thyroid cancer (TC). Summary: Specifically, in two phase II studies recently conducted on papillary TC, although the respective results were not entirely compatible as regard partial response rate and progression-free survival, sorafenib demonstrated a relatively favorable benefit/risk profile. In another more recent phase II study, whose primary endpoint was the reinduction of radioactive iodine uptake at 26 weeks, although no reinduction of radioactive iodine uptake was observed, 59% had a beneficial response and 34% had stable disease. Sorafenib hence appears to be a valid alternative to conventional treatment of metastatic papillary TC refractory to radioiodine therapy. Conclusions: Further prospective investigations are required to define the characteristics of tumor response to the drug and the factors inducing resistance to treatment. A major issue demanding immediate attention involves optimization of sorafenib treatment: this concerns multidrug combination with different tyrosine kinase inhibitors or immunomodulating agents with the aim of reducing doses and thereby improving drug tolerability and antineoplastic capability.