First experience in proteasome inhibitor therapy of dedifferentiated, radioiodine negative, somatostatin-receptor negative thyroid cancer

Objectives Despite a multimodal therapeutic approach, dedifferentiated thyroid cancer accounts for a high number of thyroid cancer associated deaths. We investigated the response of dedifferentiated thyroid cancer patients to bortezomib therapy.

Methods Six patients with progredient, metastasized, radioiodine- and somatostatin-receptor-negative thyroid cancer were included. Patients received bortezomib with a standard dose of 1,3 mg/m² on day 1, 4, 8 and 11, undergoing 3 therapeutic cycles. 18F-FDG-PET and control of thyreoglobulin levels were performed before, 6 weeks after and 6 months after therapy. Quantitative evaluation of PET scans was performed by calculation of SUV of clearly defined tumor lesions.

Results Treatment was tolerated well by all patients, adverse events included polyneurpathy and leukopenia WHO grade II. Two out of 6 patients showed decrease of thyreoglobulin levels and SUV in both posttherapeutic investigations. One patient showed a mixed response with decreasing SUV and a sligthly increasing tumor marker. Three patients had progressive disease in the follow-up.

Conclusions Proteasome inhibitor treatment is a promising therapeutic approach in dedifferentiated thyroid cancer patients. Clinical benefit was seen after bortezomib therapy in 3 out of 6 patients. This encouraging results provide rationale for further investigation to develop a specific therapeutic regime in the treatment of dedifferentiated thyroid cancer.