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High-Dose Ifosfamide Is Associated with Severe, Reversible Cardiac Dysfunction

Zenaide M.N. Quezado, MD; Wyndham H. Wilson, MD, PhD; Robert E. Cunnion, MD; Margaret M. Parker, MD; Debra Reda, BSN; George Bryant, ND; and Frederick P. Ognibene, MD
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From the Warren G. Magnuson Clinical Center and the National Cancer Institute, National Institutes of Health, Bethesda, Maryland. Requests for Reprints: Zenaide M. N. Quezado, MD, Critical Care Medicine Department, Building 10, Room 7D43, National Institutes of Health, Bethesda, MD 20892. Acknowledgments: The authors thank David W. Alling, MD, PhD, for statistical analysis; Diane Polsen, MD, Jeffrey Dichter, MD, Sophie TwoHawk, MD, and the nursing and critical care therapy staff of the 10D medical intensive care unit for their excellent care of the patients; Candace Kurtz for manuscript preparation; and Henry Masur, MD, for review of the manuscript.

Copyright ©2004 by the American College of Physicians

Ann Intern Med. 1993;118(1):31-36. doi:10.7326/0003-4819-118-1-199301010-00006
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Objective: To determine the incidence and characterize the occurrence of cardiac toxicity with high-dose ifosfamide.

Design: Retrospective chart review.

Setting: Biomedical research referral center.

Patients: Fifty-two consecutive patients with advanced lymphoma or carcinoma enrolled in phase I trials of high-dose ifosfamide as part of combination chemotherapy with autologous bone marrow transplantation.

Interventions: Patients were given escalating doses (10 to 18 g/m2) of ifosfamide in combination with carboplatin and etoposide or with lomustine and vinblastine.

Measurements: The chart review focused on clinical, radiographic, or electrocardiographic evidence of cardiovascular dysfunction. Data from invasive hemodynamic monitoring, radionuclide cineangiography, and echocardiography were also reviewed.

Results: Nine of the patients treated with ifosfamide developed congestive heart failure (17%; 95% CI, 8% to 30%). Eight of these patients, experiencing dyspnea, tachycardia, weight gain, and signs of pulmonary edema, required admission to an intensive care unit. Left ventricular contractility was found to be depressed when evaluated by radionuclide cineangiography, echocardiography, or both. Most patients responded to diuretic, vasodilator, and inotropic therapies. Two patients developed malignant ventricular arrhythmias. One patient died of intractable cardiogenic shock. Five patients died of multiorgan failure, despite showing improvement in left ventricular ejection fraction. Three patients survived and regained baseline left ventricular ejection fraction.

Conclusions: High-dose ifosfamide is associated with severe but usually reversible myocardial depression and malignant arrhythmias.





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