14065 Background: RET receptor tyrosin kinase activity plays a major role in medullary thyroid cancer (MTC) tumor growth. Sorafenib is an oral agent that selectively targets RET tyrosine kinases. Methods: 5 patients (pts) with metastatic MTC with excessive elevation of calcitonin(CTN) serum levels entered this pilotstudy. Hypercalcitonemia-related symptoms were present in all pts (3 severe diarrhea, 2 moderate) and metastasis- related symptoms were present in 4 pts (2 severe pain, 2 moderate). All pts had had prior thyreoidectomy and cervical +- mediastinal lymphnode dissection, 4 pts had prior octreotide therapy, 3 prior chemotherapy. Pts received 800 mg or 400 mg (weight < 50 kg) Sorafenib as a starting dose. According to the protocol, the dose was reduced gradually in 200 mg scale when pts revealed therapy induced side effects to avoid worsening of quality of life. Sorafenib has to be administered at least 3 months, the scheduled duration of therapy was 6 months. Physical examination, calcitonin and CEA levels were monitored every 4 weeks, measurable metastatic lesions were controlled by appropriate means 3 and 6 months after starting therapy. Primary objective was to assess the effect on CTN dependent symptoms, second objectives included assessments of tumor response (RECIST) and biochemical response. Results: After 2–3 months CTN decreased to levels >50% of baseline in all pts, to levels >90% in 2 pts. According to that all pts were free of CTN related symptoms after 4 weeks. In 4 pts CEA levels reacted in a similar way. After 6 months controls of metastatic lesions were classified as CR-1 pt, PR-1 pt, NC-3 pts. 2 pts with severe metastasis-related pain were off analgesics after 3 months of treatment. Due to side effects Sorafenib dosage was reduced to 50% of the initial dose in all patients. Interestingly marked TSH - elevations were observed in 3 pts which indicates a direct influence to the hypothalamic-pituary-axis. Conclusion: Sorafenib has to be considered as an effective teatment of symptomatic, metastatic MTC. No significant financial relationships to disclose.

No abstract

No abstract

No abstract