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

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gupta-Abramson, V. Articles by Brose, M. S. Search for Related Content PubMed PubMed Citation Articles by Gupta-Abramson, V. Articles by Brose, M. S. Related Articles Related Articles Related Editorial Social Bookmarking                            What's this?

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.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

Related Articles

• Axitinib Is an Active Treatment for All Histologic Subtypes of Advanced Thyroid Cancer: Results From a Phase II Study
  Ezra E.W. Cohen, Lee S. Rosen, Everett E. Vokes, Merrill S. Kies, Arlene A. Forastiere, Francis P. Worden, Madeleine A. Kane, Eric Sherman, Sinil Kim, Paul Bycott, Michael Tortorici, David R. Shalinsky, Katherine F. Liau, and Roger B. Cohen
  JCO 2008 26: 4708-4713 [Abstract] [Full Text]
• Axitinib Is an Active Treatment for All Histologic Subtypes of Advanced Thyroid Cancer: Results From a Phase II Study
  Ezra E.W. Cohen, Lee S. Rosen, Everett E. Vokes, Merrill S. Kies, Arlene A. Forastiere, Francis P. Worden, Madeleine A. Kane, Eric Sherman, Sinil Kim, Paul Bycott, Michael Tortorici, David R. Shalinsky, Katherine F. Liau, and Roger B. Cohen
  JCO 2008 26: 4708-4713 [Abstract] [Full Text]

Related Editorial

• Refractory Thyroid Cancer: A Paradigm Shift in Treatment Is Not Far Off
  David G. Pfister and James A. Fagin
  JCO 2008 26: 4701-4704 [Full Text]

This article has been cited by other articles:

				H. Hoftijzer, K. A Heemstra, H. Morreau, M. P Stokkel, E. P Corssmit, H. Gelderblom, K. Weijers, A. M Pereira, M. Huijberts, E. Kapiteijn, et al. Beneficial effects of sorafenib on tumor progression, but not on radioiodine uptake, in patients with differentiated thyroid carcinoma Eur. J. Endocrinol., December 1, 2009; 161(6): 923 - 931. [Abstract] [Full Text] [PDF]

				D. S. Hong, S. M. Sebti, R. A. Newman, M. A. Blaskovich, L. Ye, R. F. Gagel, S. Moulder, J. J. Wheler, A. Naing, N. M. Tannir, et al. Phase I Trial of a Combination of the Multikinase Inhibitor Sorafenib and the Farnesyltransferase Inhibitor Tipifarnib in Advanced Malignancies Clin. Cancer Res., November 15, 2009; 15(22): 7061 - 7068. [Abstract] [Full Text] [PDF]

				A. M. Tsimberidou, C. Vaklavas, S. Wen, D. Hong, J. Wheler, C. Ng, A. Naing, S. Tse, N. Busaidy, M. Markman, et al. Phase I Clinical Trials in 56 Patients with Thyroid Cancer: The M. D. Anderson Cancer Center Experience J. Clin. Endocrinol. Metab., November 1, 2009; 94(11): 4423 - 4432. [Abstract] [Full Text] [PDF]

				J. A Woyach and M. H Shah New therapeutic advances in the management of progressive thyroid cancer Endocr. Relat. Cancer, September 1, 2009; 16(3): 715 - 731. [Abstract] [Full Text] [PDF]

				S. I. Sherman Advances in Chemotherapy of Differentiated Epithelial and Medullary Thyroid Cancers J. Clin. Endocrinol. Metab., May 1, 2009; 94(5): 1493 - 1499. [Abstract] [Full Text] [PDF]

				J P. Couto, H Prazeres, P Castro, J Lima, V Maximo, P Soares, and M Sobrinho-Simoes How molecular pathology is changing and will change the therapeutics of patients with follicular cell-derived thyroid cancer J. Clin. Pathol., May 1, 2009; 62(5): 414 - 421. [Abstract] [Full Text] [PDF]

				R. T. Kloos, M. D. Ringel, M. V. Knopp, N. C. Hall, M. King, R. Stevens, J. Liang, P. E. Wakely Jr, V. V. Vasko, M. Saji, et al. Phase II Trial of Sorafenib in Metastatic Thyroid Cancer J. Clin. Oncol., April 1, 2009; 27(10): 1675 - 1684. [Abstract] [Full Text] [PDF]

				A. Nellore, K. Paziana, C. Ma, O. M. Tsygankova, Y. Wang, K. Puttaswamy, A. U. Iqbal, S. R. Franks, Y. Lv, A. B. Troxel, et al. Loss of Rap1GAP in Papillary Thyroid Cancer J. Clin. Endocrinol. Metab., March 1, 2009; 94(3): 1026 - 1032. [Abstract] [Full Text] [PDF]

				E. Winer, J. Gralow, L. Diller, B. Karlan, P. Loehrer, L. Pierce, G. Demetri, P. Ganz, B. Kramer, M. Kris, et al. Clinical Cancer Advances 2008: Major Research Advances in Cancer Treatment, Prevention, and Screening--A Report From the American Society of Clinical Oncology J. Clin. Oncol., February 10, 2009; 27(5): 812 - 826. [Abstract] [Full Text] [PDF]

				New Therapies for Thyroid Cancer Journal Watch Oncology and Hematology, December 2, 2008; 2008(1202): 1 - 1. [Full Text]

				D. G. Pfister and J. A. Fagin Refractory Thyroid Cancer: A Paradigm Shift in Treatment Is Not Far Off J. Clin. Oncol., October 10, 2008; 26(29): 4701 - 4704. [Full Text] [PDF]