Axitinib is an active treatment for all histologic subtypes of advanced thyroid cancer: results from a phase II study.

Abstract

PURPOSE:

Patients with advanced, incurable thyroid cancer not amenable to surgery or radioactive iodine ((131)I) therapy have few satisfactory therapeutic options. This multi-institutional study assessed the activity and safety of axitinib, an oral, potent, and selective inhibitor of vascular endothelial growth factor receptors (VEGFR) 1, 2, and 3 in patients with advanced thyroid cancer.

PATIENTS AND METHODS:

Patients with thyroid cancer of any histology that was resistant or not appropriate for (131)I were enrolled onto a single-arm phase II trial to receive axitinib orally (starting dose, 5 mg twice daily). Objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors was the primary end point. Secondary end points included duration of response, progression-free survival (PFS), overall survival, safety, and modulation of soluble (s) VEGFR.

RESULTS:

Sixty patients were enrolled. Partial responses were observed in 18 patients, yielding an ORR of 30% (95% CI, 18.9 to 43.2). Stable disease lasting > or = 16 weeks was reported in another 23 patients (38%).

OBJECTIVE:

responses were noted in all histologic subtypes. Median PFS was 18.1 months (95% CI, 12.1 to not estimable). Axitinib was generally well tolerated, with the most common grade > or = 3 treatment-related adverse event being hypertension (n = 7; 12%). Eight patients (13%) discontinued treatment because of adverse events. Axitinib selectively decreased sVEGFR-2 and sVEGFR-3 plasma concentrations versus sKIT, demonstrating its targeting of VEGFR.

CONCLUSION:

Axitinib is a selective inhibitor of VEGFR with compelling antitumor activity in all histologic subtypes of advanced thyroid cancer.

• Authors: 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, Roger B Cohen
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 26 Issue 29 Pg. 4708-13 (Oct 10 2008) ISSN: 1527-7755 [Electronic] United States
• PMID: 18541897 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Angiogenesis Inhibitors
• Antineoplastic Agents
• Imidazoles
• Indazoles
• Axitinib
• Receptors, Vascular Endothelial Growth Factor

Topics

• Adult
• Aged
• Aged, 80 and over
• Angiogenesis Inhibitors (therapeutic use)
• Antineoplastic Agents (therapeutic use)
• Axitinib
• Female
• Humans
• Imidazoles (therapeutic use)
• Indazoles (therapeutic use)
• Male
• Middle Aged
• Receptors, Vascular Endothelial Growth Factor (antagonists & inhibitors)
• Thyroid Neoplasms (drug therapy, pathology)