Effects of oral arsenic trioxide therapy on QT intervals in patients with acute promyelocytic leukemia: implications for long-term cardiac safety.
Ventricular tachyarrhythmias may occur during intravenous arsenic trioxide (As2O3). This has not happened during oral As2O3. Sixteen patients were studied by electrocardiography and 24-hour Holter monitoring at baseline, during and after oral As2O3 (As2O3-ON, As2O3-OFF). QT and corrected QT (QTc) were significantly longer during As2O3-ON than in As2O3-OFF, but QT and QTc dispersions were comparable. The patients' 24-hour heart rates were higher during As2O3-ON than in As2O3-OFF. QTc intervals at each hour were longer during As2O3-ON than in As2O3-OFF. However, QTc prolongation of more than 30 milliseconds only occurred at one time point (2 hours) after oral As2O3, resulting in QTc of more than 500 milliseconds in 3 of 16 patients, all within 4 hours of oral As2O3. Although the standard deviation of normal RR interval was lower during As2O3-ON, ratios of low frequency to high frequency power for As2O3-ON and As2O3-OFF were comparable. No ventricular proarrhythmias were observed. These observations, due to the lower peak plasma arsenic reached during oral As2O3, may explain the relative cardiac safety of oral As2O3.
Siu
Chung-Wah
CW
Divisions of Cardiology, Hematology, and Clinical Pharmacology, Department of Medicine, University of Hong Kong, Hong Kong.
Au
Wing-Yan
WY
Yung
Cindy
C
Kumana
Cyrus R
CR
Lau
Chu-Pak
CP
Kwong
Yok-Lam
YL
Tse
Hung-Fat
HF
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D064420:Drug-Related Side Effects and Adverse Reactions; D004562:Electrocardiography; D015716:Electrocardiography, Ambulatory; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000175:diagnosis* / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010087:Oxides / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use; D016896:Treatment Outcome
D001152:Arsenicals; D010087:Oxides; D000077237:Arsenic Trioxide