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Effect of Arsenic Trioxide on QT Interval in Patients With Advanced Malignancies

Jean T. Barbey, John C. Pezzullo, Steven L. Soignet

From the Department of Medicine, Georgetown University, Washington, DC; the Arcus Group, New York, the Department of Medicine, Memorial Sloan-Kettering Cancer Center, and the Joan and Sanford I. Weill Medical College of Cornell University, New York, NY.

Address reprint requests to Jean T. Barbey, MD, Department of Medicine, Georgetown University, 3900 Reservoir Rd, NW, MedDent Building, C 305, Washington, DC 20007; e-mail: tczjb{at}aol.com.

Purpose: Arsenic trioxide is an effective treatment for patients with acute promyelocytic leukemia (APL) who have relapsed from or are refractory to all-trans-retinoic acid and anthracycline chemotherapy. Since arsenic can prolong the QT interval and lead to torsade de pointes, a life-threatening ventricular arrhythmia, this retrospective analysis was conducted to determine the degree of QT prolongation in patients treated with arsenic trioxide.

Patients and Methods: Clinical data and serial ECGs from 99 patients with advanced malignancies who received 170 courses of arsenic trioxide in either a phase I or phase II investigational study were reviewed.

Results: Prolonged QT intervals developed in 38 patients (26 patients had intervals 500 milliseconds). Compared with baseline, the heart rate—corrected (QTc) interval was prolonged by 30 to 60 milliseconds in 36.6% of treatment courses, and by more than 60 milliseconds in 35.4% of patients. The degree of prolongation was higher in men than in women during the first course of therapy, and in patients with hypokalemia. In patients receiving multiple courses, QTc intervals returned to pretreatment levels before the second course, signifying that arsenic trioxide does not permanently prolong the QTc interval. One hypokalemic, arsenic trioxide–treated patient with relapsed APL developed asymptomatic torsade de pointes, which resolved spontaneously and did not recur after electrolyte replacement. There were no sudden or arrhythmia-related deaths.

Conclusion: This analysis shows that arsenic trioxide can prolong the QTc interval. However, with appropriate ECG monitoring and management of electrolytes and concomitant medications, arsenic trioxide can be safely administered in patients with relapsed APL.

This study was supported by research funding from Cell Therapeutics Inc, Seattle, WA.

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