Elsevier

Progress in Cardiovascular Diseases

Volume 53, Issue 2, September–October 2010, Pages 94-104
Progress in Cardiovascular Diseases

Cardiac Toxicity From Systemic Cancer Therapy: A Comprehensive Review

https://doi.org/10.1016/j.pcad.2010.05.006Get rights and content

Abstract

Cardiovascular toxicity is a potential short- or long-term complication of anticancer therapy. Exposure to chemotherapy medications, primarily the anthracycline class, can lead to potentially irreversible clinically significant cardiac dysfunction. The advent of novel biologic agents, including monoclonal antibodies and tyrosine kinase inhibitors, has revolutionized the treatment of several types of malignancies. Although targeted therapies are considered less toxic and better tolerated by patients compared with classic chemotherapy agents, rare serious complications have been observed; and longer-term follow-up is needed to determine the exact profile of related cardiac adverse effects. Cardiac toxicity associated with cancer therapies can range from asymptomatic subclinical abnormalities, including electrocardiographic changes and temporary left ventricular ejection fraction decline, to life-threatening events such as congestive heart failure or acute coronary syndromes. Assessment of the prevalence, type, and severity of cardiac toxicity caused by various cancer treatments is a critical topic for patient management and specifically for new drug development. Guidelines for monitoring cardiac adverse effects have been formulated; however, appropriate supportive evidence remains limited. Given the rate of new drug development designed to fulfill unmet oncologic needs, efforts are needed to promote strategies for cardiac risk detection and management and to avoid unintended consequences potentially impeding development of, regulatory approval for, and patient access to novel therapies. These advances require ongoing research to assess and manage the cardiovascular safety of patients treated with anticancer agents, as well as a well-organized collaboration between oncologists and cardiologists. The aim of this review is to summarize potential cardiovascular toxicities for a range of cancer chemotherapeutics and to review general mechanisms of cardiovascular toxicity for each agent.

Section snippets

Left ventricular dysfunction

Left ventricular dysfunction (LVD) is associated with exposure to several anticancer therapies. An early definition of the effect of cancer therapy on LV function has been promulgated by the Cardiac Review and Evaluation Committee supervising trastuzumab (Herceptin) clinical trials.1 According to this definition, cardiomyopathy is characterized by a “decrease in cardiac left ventricular ejection fraction (LVEF) that was either global or more severe in the septum; (2) symptoms of congestive

Cardiac ischemia

Although cardiac ischemia related to chemotherapy administration is an unusual occurrence, an increased risk of acute coronary syndrome has been associated with administration of cytotoxic and targeted agents for cancer treatment.

Hypertension

Multiple investigative and clinical observations have demonstrated hypertension to be a common class effect resulting from treatment with VEGF inhibitors.75 Rates of significant hypertension appear to depend on the antiangiogenic agent used, the tumor type, and patient-related factors including age and comorbidity (Table 3). In the major trials using bevacizumab, rates of significant toxicity ranged from 7% to 36%.42, 45, 46, 47 The degree of hypertension associated with the VEGFR tyrosine

QT prolongation

Prolongation of the QT interval can lead to life-threatening cardiac arrhythmias, including “torsades de pointes” (TdP). Although prolongation of the QT interval is not the best predictor of proarrhythmic risk, it represents the principal clinical surrogate marker by which to evaluate the arrhythmic risk of a drug; and it has led to withdrawal of several anticancer drugs from the market. Although drugs leading to prolonged QT may possess significant risks of serious adverse events, the clinical

Conclusions

Within the oncologic toolbox are both traditional and novel anticancer agents with the potential to induce cardiac toxicity. Oncologists thus have had to develop the ability to identify and manage complicated cardiac risks in clinical investigations and in general practice. Many highly effective agents in contemporary oncology, including anthracyclines and trastuzumab, are associated with well-described risks of short- and long-term cardiac events. As these agents are often used with curative

Statement of Conflict of Interest

All authors declare that there are no conflicts of interest.

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    Statement of Conflict of Interest: see page 101.

    1

    The first 2 authors equally contributed to the manuscript.

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