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Cancer Therapy: Clinical |
Authors' Affiliations: 1 Center for Cancer Research and 2 Cancer Therapeutics Evaluation Program, National Cancer Institute and 3 National Heart Lung and Blood Institute, NIH, Bethesda, Maryland
Requests for reprints: Richard L. Piekarz, Center for Cancer Research, National Cancer Institute, Room 12N226, Building 10, 10 Center Drive MSC 1903, Bethesda, MD 20892-1903. Phone: 301-402-3524; Fax: 301-402-1608; E-mail: rpiekarz{at}nih.gov.
Purpose: The histone deacetylase inhibitor depsipeptide (FK228) has activity in patients with cutaneous or peripheral T-cell lymphoma. Electrocardiogram abnormalities, thought to be a class effect, were observed in preclinical animal studies and phase I testing and led to the incorporation of intensive cardiac monitoring in an ongoing efficacy trial.
Patients and Methods: This report summarizes the cardiac monitoring of 42 patients enrolled and treated on a phase II trial with depsipeptide. Cardiac evaluations included serial electrocardiograms to evaluate T-wave, ST segment, and QT interval effects and serial serum cardiac troponin I levels and left ventricular ejection fraction (LVEF) evaluations to exclude myocardial damage.
Results: Cardiac studies from 282 cycles and 736 doses of depsipeptide included 2,051 electrocardiograms and 161 LVEF evaluations. Although T-wave flattening (grade 1) or ST segment depression (grade 2) was observed in more than half of the electrocardiograms obtained posttreatment, these electrocardiogram abnormalities were not associated with elevation of cardiac troponin I or with altered left ventricular function. No significant changes in LVEF were observed, even in 16 patients treated for 
6 months and regardless of prior anthracycline exposure. Posttreatment electrocardiograms had a mean heart rate–corrected QT interval prolongation of 14.4 milliseconds compared with baseline. Electrolyte replacement has been instituted to mitigate potential untoward effects.
Conclusion: The data obtained in this study show that the administration of depsipeptide is not associated with myocardial damage or impaired cardiac function. The potential effect of heart rate–corrected QT interval prolongation remains under study.
Commentary
Clin. Cancer Res. 2006 12: 3646-3647.
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