Phase II trial of sorafenib in advanced thyroid cancer.

Abstract

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.

• Authors: 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
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 26 Issue 29 Pg. 4714-9 (Oct 10 2008) ISSN: 1527-7755 [Electronic] United States
• PMID: 18541894 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Benzenesulfonates
• Phenylurea Compounds
• Pyridines
• Niacinamide
• Sorafenib

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents (therapeutic use)
• Benzenesulfonates (therapeutic use)
• Female
• Humans
• Male
• Middle Aged
• Niacinamide (analogs & derivatives)
• Phenylurea Compounds
• Pyridines (therapeutic use)
• Sorafenib
• Thyroid Neoplasms (drug therapy, pathology)