Chemotherapy-Associated Cardiotoxicity: How Often Does it Really Occur and How Can it Be Prevented?
Section snippets
Anthracyclines
Anthracyclines are among the most commonly used chemotherapeutic agents, with antineoplastic activity against a wide variety of tumors. In particular, they represent a cornerstone of chemotherapy for lymphomas, hematologic malignancies, breast carcinomas, and sarcomas.
Almost since the time that anthracycline use began, the presence of a dose-dependent rate of cardiotoxicity has been recognized.1, 2, 3, 4, 5 Early reports examined the levels of clinical cardiotoxicity, usually manifesting as
Anti-HER2 Targeted Therapy: Trastuzumab and Lapatinib
Besides the anthracycline drugs, no other cancer medication has been studied in more detail for left ventricular dysfunction than trastuzumab. Trastuzumab is a monoclonal antibody against HER2, an epidermal growth factor receptor family member overexpressed in 20% to 25% of breast cancers.27 HER2 overexpression/amplification connotes a more aggressive tumor with increased rates of metastasis and mortality.27
In addition to its role in breast cancer, HER2 is an important growth factor receptor in
Preventing cardiotoxicity with coadministration of cardiac medications
Standard medical treatment for heart failure uses similar strategies regardless of the underlying cause of the cardiomyopathy. Although older treatments (digoxin, diuretics) were focused on treating the symptoms of heart failure, therapy over the past 3 decades has increasingly focused on neurohormonal antagonism (eg, β-blockers, angiotensin-converting enzyme inhibitors [ACE-Is], angiotensin II receptor blockers [ARBs], aldosterone antagonists).6 The neurohormonal antagonist strategy focuses on
Definitions of left ventricular dysfunction and heart failure
Much of the confusion regarding how to classify cardiotoxicity manifesting as either asymptomatic drops in LVEF or as symptomatic heart failure is attributable to internal confusion in the consensus criteria. In the current “Common Terminology Criteria for Adverse Events (CTCAE) version 4.0,” the same toxicity is listed under three separate headings, and the definition contradicts each another.54 For example, an individual who experienced an asymptomatic treatment-emergent drop in LVEF from 60%
Summary
With the tremendous growth in effective antineoplastic agents, a concomitant concerning increase has occurred in off-target side effects. Cardiotoxicity, and specifically left ventricular dysfunction, remains the limiting factor for many of these agents, and is the focus of growing research and clinical emphasis.
Ultimately winning the battle to allow patients to safely receive indicated doses of increasingly effective anti-neoplastic therapies will require the following conditions:
- 1.
Consistent
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