Pharmacologic measures in the prevention of left ventricular dysfunction associated with molecular-targeted therapies in the treatment of cancer patients

ABSTRACT

Introduction: Left ventricular dysfunction (LVD) is an infrequent but significant side effect of certain molecular-targeted cancer therapies and may lead to treatment modification and impact on disease prognosis. There may be a role for beta blockers (BB), angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) in the prevention of LVD.

Areas covered: There are multiple definitions for LVD based on clinical and/or imaging features. Molecular-targeted therapies cause reversible LVD. Therapies with well-reported LVD are inhibitors of human epidermal growth factor 2 (HER2), angiogenesis, Abelson murine leukemia viral oncogene homolog (ABL) and the proteasome. BB, ACEI and ARB seem to have a role in the prevention of LVD associated with anthracyclines. Few trials have investigated the role of BB, ACEI and ARB as primary prevention of LVD in molecular-targeted therapies. Their results are not conclusive but a beneficial role cannot be excluded.

Expert opinion: Because of inconclusive data, future interventional studies should not include all treated patients with molecular-targeted therapy, but focus on patients at risk for developing LVD. Another option is to study patients who show early signs of LVD to prevent progression to overt heart failure.

KEYWORDS:

• Cancer
• left ventricular dysfunction
• prevention
• targeted therapy
• beta blocker
• angiotensin converting enzyme inhibitor
• angiotensin receptor blocker

Article highlights

Several molecular-targeted therapies are associated with left ventricular dysfunction.

• Molecular-targeted therapies cause mainly a myocardial dysfunction that is largely reversible after interruption of the drug. A rechallenge is in some cases possible.

• Left ventricular dysfunction has been described with HER2 inhibitors (e.g. trastuzumab), angiogenesis inhibitors (e.g. bevacizumab, tyrosine kinase inhibitors) and ABL inhibitors (e.g. imatinib).

• Studies with anthracyclines have suggested a role for beta blockers, angiotensin converting enzyme inhibitors and angiotensin receptor blockers in the prevention of left ventricular dysfunction. Available data with molecular-targeted therapies suggest a possible cardioprotective role, but this needs confirmation in well-designed large trials including patients with high cardiac risk.This box summarizes key points contained in the article

Declaration of interest

The authors were supported by the European Chemical Agency. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper was not funded.