Cardiac Effects of Cancer Therapy

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Cardiac Effects of Cancer Therapy Haoyi Zheng, Boris Kobrinsky, Stuart Katz, and James L. Speyer

SUMMARY

O F

K E Y

P O I N T S

Incidence

Cardiomyopathy/Chronic Heart Failure • Anthracyclines: cardiomyopathy/ chronic heart failure occurs in 5% to 20% of patients receiving cumulative doxorubicin (more than 450 mg/m2); the incidence is higher in children • Other antineoplastics (e.g., mitoxantrone and cyclophosphamide): the incidence of cardiomyopathy/chronic heart failure is less than 2% • Ifosfamide • Trastuzumab (not common as a single agent; increased risk with anthracycline) • Pertuzumab • Imatinib • Lapatinib • Sunitinib • Radiation therapy: cardiomyopathy/ chronic heart failure is common 5 to 20 years after use of a single anteroposterior port QT Prolongation • Arsenic trioxide (a black box warning from the U.S. Food and Drug Administration [FDA]) • Romidepsin • Vorinostat • Pazopanib • Vandetanib (a black box warning from the FDA) • Crizotinib • Nilotinib (a black box warning from the FDA) • Vemurafenib • Eribulin Myocardial Ischemia • Radiation therapy • 5-Fluorouracil: 1% to 4.5% with infusion schedules • Capecitabine

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Edema • Docetaxel, interleukins, interferons, tumor necrosis factor, cytokines, granulocyte-macrophage colonystimulating factor, monoclonal antibody (CD20) • Dasatinib • All-trans retinoic acid Hypertension • Bevacizumab • Pazopanib • Sorafenib • Sunitinib • Vandetanib Hypotension • Interleukins • Tumor necrosis factor • Granulocyte-macrophage colonystimulating factor Pericardial Disease • Radiation therapy: effusions in 6% to 30% of patients receiving radiation therapy directed at the chest; constriction in 2% of patients receiving radiation therapy directed at the chest with current techniques • Cardiac tamponade • Endocardial fibrosis • Busulfan Etiology of Complications • Anthracycline-induced cardiomyopathy • HER2 signaling pathway and decreased repair • Radiation-induced cardiomyopathy • Radiation-induced myocardial ischemia • Endothelial dysfunction • Decreased systemic vascular resistance Diagnosis • Clinical cardiac symptoms— American Heart Association/

American College of Cardiology staging, New York Heart Association classification, and Common Terminology Criteria for Adverse Events for Heart Failure • Radionuclide scans—serial scans including baseline • Endomyocardial biopsy—Billingham histopathological grading system • Echocardiography—pericardial effusion/constriction, left ventricular systolic/diastolic dysfunction • Cardiac magnetic resonance imaging—left ventricular systolic/ diastolic dysfunction, myocardial fibrosis/necrosis detected by late gadolinium enhancement • Troponin (T or I) • Natriuretic peptide Treatment Cardiomyopathy/Congestive Heart Failure • Sodium and fluid restriction • Diuretics • Angiotensin-converting enzyme inhibitors or angiotensin receptor blocking agents • β-Blockers • Discontinue offending agent Risk Reduction with Anthracyclines • Anthracyclines: limit dose (e.g., doxorubicin: <450 mg/m2); use less-toxic analogs • Alteration of dose schedule • Unique delivery systems (e.g., liposomes) • Pegylated liposomal doxorubicin • Blocking agent: dexrazoxane (Zinecard) Radiation-Induced Pericardial Disease • Acute pericarditis: nonsteroidal antiinflammatory drugs, steroids • Constriction: pericardiectomy