Originally published as JCO Early Release 10.1200/JCO.2008.16.3279 on June 9 2008

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Phase II Trial of Sorafenib in Advanced Thyroid Cancer

Vandana Gupta-Abramson, Andrea B. Troxel, Anoma Nellore, Kanchan Puttaswamy, Maryann Redlinger, Kathy Ransone, Susan J. Mandel, Keith T. Flaherty, Laurie A. Loevner, Peter J. O'Dwyer, Marcia S. Brose

From the Developmental Therapeutics Program of the Abramson Cancer Center and Departments of Medicine, Biostatistics and Epidemiology, Otorhinolaryngology: Head and Neck Surgery, and Radiology, University of Pennsylvania, Philadelphia, PA

Corresponding author: Marcia S. Brose, MD, PhD, The University of Pennsylvania, Abramson Cancer Center, Department of Otorhinolaryngology: Head and Neck Surgery, Department of Medicine, Division of Hematology/Oncology, Clinical Research Building, Room 127, 415 Curie Blvd, Philadelphia, PA 19104; e-mail: brosem{at}mail.med.upenn.edu

Purpose Given the molecular pathophysiology of thyroid cancer and the spectrum of kinases inhibited by sorafenib, including Raf kinase, vascular endothelial growth factor receptors, platelet-derived growth factor receptor, and RET tyrosine kinases, we conducted an open-label phase II trial to determine the efficacy of sorafenib in patients with advanced thyroid carcinoma.

Patients and Methods Eligible patients with metastatic, iodine-refractory thyroid carcinoma received sorafenib 400 mg orally twice daily. Responses were measured radiographically every 2 to 3 months. The study end points included response rate, progression-free survival (PFS), and best response by Response Evaluation Criteria in Solid Tumors.

Results Thirty patients were entered onto the study and treated for a minimum of 16 weeks. Seven patients (23%; 95% CI, 0.10 to 0.42) had a partial response lasting 18+ to 84 weeks. Sixteen patients (53%; 95% CI, 0.34 to 0.72) had stable disease lasting 14 to 89+ weeks. Seventeen (95%) of 19 patients for whom serial thyroglobulin levels were available showed a marked and rapid response in thyroglobulin levels with a mean decrease of 70%. The median PFS was 79 weeks. Toxicity was consistent with other sorafenib trials, although a single patient died of liver failure that was likely treatment related.

Conclusion Sorafenib has clinically relevant antitumor activity in patients with metastatic, iodine-refractory thyroid carcinoma, with an overall clinical benefit rate (partial response + stable disease) of 77%, median PFS of 79 weeks, and an overall acceptable safety profile. These results represent a significant advance over chemotherapy in both response rate and PFS and support further investigation of this agent in these patients.

published online ahead of print at www.jco.org on June 9, 2008.

Supported by the Templeton Family Cancer Research Fund, the Damon Runyon Cancer Research Foundation (CI-25-05; M.S.B.), and Grants No. 1K08CA090431 (M.S.B.) and K12-CA-076931 (V.G.-A.) from the National Institutes of Health/National Cancer Institute.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Clinical trial information can be found for the following: UPCC-03305.

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