Rapid response to sorafenib in metastatic medullary thyroid carcinoma.

Objective: To investigate the efficacy of sorafenib in progressive metastatic Medullary Thyroid Carcinoma (MTC), for which there is currently no effective treatment.

Design: Off-label observational study.

Methods: Sorafenib 400 mg twice daily was evaluated. The primary endpoint was the objective Response Evaluation Criteria in Solid Tumours (RECIST) score assessed on day 28 and every 12 weeks thereafter. Additional endpoints were time to response, duration of tumour response, tumour-related symptoms, and changes in tumour markers, calcitonin, and CEA measured initially, at 2 weeks, and then every 4 weeks. Therapy duration was 2 weeks, and 3-12 months.

Results: The 5 patients meeting study criteria received sorafenib 400 mg orally twice a day until disease progression or unacceptable toxicity developed. 2 patients showed a partial response with tumour regression of -46% and -36% after 6 and 9 months, respectively, and 2 patients exhibited tumour regression of -14% and -29%, respectively (stable disease). Ultrasound-documented regression of -37% within 2 weeks occurred in 1 patient. Calcitonin decreased within 2 weeks in all patients by -69, -90, -75, -96, and -39%, respectively. 1 patient died because of progressive ascites from acute renal and hepatocellular failure. 2 patients developed grade 3 hand-foot syndrome within the first month, so that sorafenib was interrupted or reduced; other side effects were rash, fatigue, and hair loss. 3 patients remain on sorafenib, 2 at a reduced dosage (600 mg/d).

Conclusion: These data suggest a possible role for sorafenib in the treatment of progressive metastatic MTC.