Clinical review: kinase inhibitors: adverse effects related to the endocrine system

J Clin Endocrinol Metab. 2013 Apr;98(4):1333-42. doi: 10.1210/jc.2012-4085. Epub 2013 Feb 28.

Abstract

Context: The use of kinase inhibitors (KIs) in the treatment of cancer has become increasingly common, and practitioners must be familiar with endocrine-related side effects associated with these agents. This review provides an update to the clinician regarding the management of potential endocrinological effects of KIs.

Evidence acquisition: PubMed was employed to identify relevant manuscripts. A review of the literature was conducted, and data were summarized and incorporated.

Evidence synthesis: KIs, including small molecule KIs and monoclonal antibodies directed against kinases, have emerged over the past decade as an important class of anticancer agents. KIs specifically interfere with signaling pathways that are dysregulated in certain types of cancers and also target common mechanisms of growth, invasion, metastasis, and angiogenesis. Currently, at least 20 KIs are approved as cancer therapeutics. However, KIs may affect a broad spectrum of targets and may have additional, unidentified mechanisms of action at the cellular level due to overlap between signaling pathways in the tumor cell and endocrine system. Recent reports in the literature have identified side effects associated with KIs, including alterations in thyroid function, bone metabolism, linear growth, gonadal function, fetal development, adrenal function, and glucose metabolism.

Conclusions: Clinicians need to monitor the thyroid functions of patients on KIs. In addition, bone density and vitamin D status should be assessed. Special care should be taken to follow linear growth and development in children taking these agents. Clinicians should counsel patients appropriately on the potential adverse effects of KIs on fetal development.

Publication types

  • Evaluation Study
  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Antineoplastic Agents / adverse effects
  • Drug-Related Side Effects and Adverse Reactions / chemically induced
  • Drug-Related Side Effects and Adverse Reactions / therapy*
  • Endocrine System / drug effects*
  • Endocrine System / physiology
  • Endocrine System Diseases / chemically induced*
  • Endocrine System Diseases / therapy*
  • Female
  • Fertility / drug effects
  • Fertility / physiology
  • Humans
  • Jaw Diseases / chemically induced
  • Jaw Diseases / epidemiology
  • Jaw Diseases / therapy
  • Osteonecrosis / chemically induced
  • Osteonecrosis / epidemiology
  • Osteonecrosis / therapy
  • Pregnancy
  • Protein Kinase Inhibitors / adverse effects*
  • Protein Kinase Inhibitors / therapeutic use
  • Thyroid Gland / drug effects
  • Thyroid Gland / physiology

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors