Current evidence on thyroid related adverse events in patients treated with protein tyrosine kinase inhibitors

Drug Metab Rev. 2019 Nov;51(4):562-569. doi: 10.1080/03602532.2019.1687512. Epub 2019 Nov 13.

Abstract

Tyrosine kinase inhibitors (TKI) are gaining more ground in oncology, they are widely used in the treatment of multiple types of cancers; still important side effects limit their efficacy. The aim of this study is to evaluate the existing medical literature on TKI induced thyroid dysfunction, to assess the adverse effects of targeted therapy on thyroid function in oncological patients and to evaluate the effects of thyroid dysfunction on disease prognosis. We included in this review 22 original studies published between 2010 and 2019. We used the PubMed database to search for articles upon the development of hypothyroidism and hyperthyroidism in TKI treated patients. After a careful review of the existing literature, we selected the relevant studies and cross-referenced the bibliography of each paper. A number of 1641 patients were included in our review. We found that thyroid dysfunction is not a rare side effect of TKI treatment, approximately 33% of the total number of patients presented clinical hypothyroidism. We also studied the necessity of thyroid hormone substitution treatment, a quarter of evaluated patients needed substitution therapy. Multiple studies showed that there is a link between a patient developing hypothyroidism and progression free survival. Hypothyroidism is a frequent side effect of TKI treatment, which affects the quality of life, sometimes even determines physicians to stop TKI treatment altogether. Our study underlines the necessity of TSH baseline testing and monitoring in patients treated with TKI agents.

Keywords: TKIs; Tyrosine kinase inhibitors; hypothyroidism; progression free survival; thyroid dysfunction.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Humans
  • Hyperthyroidism / chemically induced*
  • Hypothyroidism / chemically induced*
  • Neoplasms / drug therapy
  • Neoplasms / enzymology
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / adverse effects*

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors