Thyroid dysfunctions induced by tyrosine kinase inhibitors

Expert Opin Drug Saf. 2014 Jun;13(6):723-33. doi: 10.1517/14740338.2014.913021. Epub 2014 May 12.

Abstract

Introduction: Recently, tyrosine kinase inhibitors (TKIs) have emerged as a new class of anticancer therapy. Although generally considered less toxic than cytotoxic chemotherapy, TKIs do cause significant side effects including fatigue and hypertension. In addition, thyroid dysfunction is a well-known adverse effect of TKI.

Areas covered: This review provides a comprehensive assessment of TKI-induced thyroid dysfunctions by sunitinib, sorafenib, pazopanib, imatinib, dasatinib, nilotinib, vandetanib, axitinib, motesanib and tivozanib. Furthermore, the potential mechanisms that result in this toxicity, the clinical impact of thyroid dysfunction in these patients and the controversies regarding treatment with thyroid hormone (TH) therapy are evaluated.

Expert opinion: Detection of TKI-induced thyroid dysfunction requires routine monitoring of thyroid function and may necessitate treatment. Potential benefits in developing thyroid dysfunction and potential harm in treating it necessitate controlled studies. Finally, if treatment is pursued, appropriate dosing and timing of TH replacement will require prospective clinical evaluation.

Keywords: axitinib; dasatinib; hyperthyroidism; hypothyroidism; imatinib; motesanib; nilotinib; pazopanib; sorafenib; sunitinib; thyroid cancer; thyroid dysfunctions; tivozanib; tyrosine kinase inhibitors; vandetanib.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / therapeutic use
  • Drug Monitoring / methods
  • Humans
  • Protein Kinase Inhibitors / adverse effects*
  • Protein Kinase Inhibitors / therapeutic use
  • Thyroid Diseases / chemically induced*
  • Thyroid Diseases / physiopathology
  • Thyroid Function Tests / methods
  • Thyroid Hormones / administration & dosage

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Thyroid Hormones