Sorafenib stops disease progression in the majority of patients with advanced differentiated thyroid cancer refractory to radioactive iodine.
V. Marotta1, V. Ramundo1, M. Del Prete1, F. Marciello1, G. Palmieri1, L. Camera1, M. Vitale2, A. Colao1 & A. Faggiano1,3
Differentiated thyroid cancers (DTC) have an excellent prognosis with a 10 year disease-related survival of 85%. However, about 5% of DTC patients develop an aggressive disease with distant metastasis and loss of radioactive iodine (RAI) avidity. An effective treatment is not available for these patients and survival rates are less than 15%. The MAP-kinase pathway is strikingly involved in the pathogenesis of DTC. This is why compounds striking the MAP-Kinase pathway may be useful for treatment of advanced DTC refractory to RAI.
A phase II clinical trial was designed to assess efficacy and safety of the Tyrosine-Kinase inhibitor Sorafenib in 9 patients with progressive RAI-refractory DTC. Median follow-up period was 10 months. Sorafenib was administered at a starting dose of 400 mg b.d. Computed tomography scans were performed at baseline and at 12-weeks intervals to assess radiologic responses. Determination of Tg was performed at 4 weeks intervals to assess biochemical response. Patients were subjected to clinical and biochemical examinations at 4-weeks intervals to assess the occurrence of adverse events (AE).
In eight patients (89%) disease progression was arrested. According to RECIST criteria, 5 of them achieved a stable disease (56%) and 3 a parzial response (33%). Five out of 8 responding patients (62%) had a durable response. In all responding patients a dramatic drop in Tg levels was observed with a median time of nadir of 60 days. The most prevalent AE were hand-foot syndrome (87%), TSH increase (75%), asthenia and arthralgia (75%), hypertension (50%), anemia (37,5%), alopecia (25%). Only one patients stopped treatment because of toxicity. Toxicities were fully controlled by halving the dosage in 7 patients (77,7%).
Sorafenib is effective in controlling disease progression in the majority of patients with advanced DTC refractory to RAI, also resulting in objective response in one third of them.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.