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Cancer Chemotherapy and Pharmacology
Published in: Cancer Chemotherapy and Pharmacology 6/2014

Open Access 01-12-2014 | Original Article

A Phase II trial of axitinib in patients with various histologic subtypes of advanced thyroid cancer: long-term outcomes and pharmacokinetic/pharmacodynamic analyses

Authors: E. E. W. Cohen, M. Tortorici, S. Kim, A. Ingrosso, Y. K. Pithavala, P. Bycott

Published in: Cancer Chemotherapy and Pharmacology | Issue 6/2014

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Abstract

Purpose

Axitinib, a potent and selective second-generation inhibitor of vascular endothelial growth factor receptors, has shown activity in advanced thyroid cancer in a Phase II study. We report updated overall survival and pharmacokinetic/pharmacodynamic (PK/PD) analyses from the study.

Methods

Patients (N = 60) with advanced thyroid cancer of any histology for whom iodine-131 (131I) failed to control the disease or 131I was not appropriate therapy were administered axitinib 5 mg twice daily. Objective response rate (primary endpoint), duration of response, progression-free survival, overall survival, safety, and PK/PD relationships were assessed.

Results

Objective response rate was 38 % [23 partial responses; 95 % confidence interval (CI) 26–52], and 18 (30 %) patients had stable disease lasting ≥16 weeks. Responses occurred in all histologic subtypes. With median follow-up of 34 months (95 % CI 32–37), median overall survival was 35 months (95 % CI 19–not estimable), median progression-free survival was 15 months (95 % CI 10–20), and median duration of response was 21 months (95 % CI 13–46). Most common Grade 3/4 treatment-related adverse events included hypertension (13 %), proteinuria (8 %), diarrhea (7 %), weight decrease (7 %), and fatigue (5 %). PK/PD analyses revealed trends toward greater tumor size reduction and response probability with higher axitinib plasma exposures.

Conclusions

Axitinib appears active and well tolerated in patients with various histologic subtypes of advanced thyroid cancer, demonstrating durable responses and long overall survival. Axitinib may be useful for the treatment of advanced thyroid cancer.
Appendix
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Metadata
Title
A Phase II trial of axitinib in patients with various histologic subtypes of advanced thyroid cancer: long-term outcomes and pharmacokinetic/pharmacodynamic analyses
Authors
E. E. W. Cohen
M. Tortorici
S. Kim
A. Ingrosso
Y. K. Pithavala
P. Bycott
Publication date
01-12-2014
Publisher
Springer Berlin Heidelberg
Published in
Cancer Chemotherapy and Pharmacology / Issue 6/2014
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-014-2604-8

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