Usefulness of sorafenib in the management of advanced thyroid carcinoma
Gabriel Obiols, Jaume Capdevila, Carles Zafon & Jordi Mesa
One of the most important activating genetic aberrations in differentiated thyroid cancer (DTC) development pathways involves the RET/PTCRASRAFMAPK axis. Mutations in the RET gene are essential in medullary thyroid carcinoma (MTC). Sorafenib is the first compound to reach clinical practice that is capable of inhibiting all the RAF kinases. Moreover, it targets a panel of tyrosine kinase receptors, such as VEGF receptors which gives to sorafenib not only proapoptotic, but also antiangiogenic properties.
Aim: To investigate the usefulness of sorafenib in the treatment of thyroid cancer.
Patients and methods: Eleven patients (6 MTC, 4 DTC, 1 anaplastic carcinoma) with advanced disease (distant metastases) have been treated with sorafenib (age at diagnosis 2280 years; follow-up from diagnosis 118 years; duration of treatment 237 months).
To evaluate the response, we have used RECIST criteria and thyroglobulin (TG) (in DTC and anaplastic) or calcitonin (CT) and carcinoembryonic antigen (CEA) (in MTC) measurements.
Results: Four MTC cases have shown partial response (PR) with tumour volume reductions from 30 to 55%. Median CT levels decreased from 35 269 to 13 420 pg/ml and CEA from 260 to 115 ng/ml. Two cases have stable disease (SD); CT decreased from 9805 to 5579 and from 65 495 to 36 397 pg/ml and CEA from 52 to 32 and from 2104 to 894 ng/ml.
Three patients with DTC showed SD; median TG decreased from 1280 to 622 ng/ml. Two patients, including a follicular variant papillary TC and the anaplastic carcinoma, experienced a progressive disease with tumours increasing 53 and 29% respectively, but with a reduction in Tg levels (from 137 to 107, and from 65 to 32 ng/ml).
The most frequent side effects were handfoot syndrome (8), oral mucositis (10) and diarrhoea (8).
Conclusion: Sorafenib could be useful in advanced thyroid carcinoma. MTC appears to have a better response than DTC.