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Prevalence, management, and clinical consequences of QT interval prolongation during treatment with arsenic trioxide.

AbstractPURPOSE:
Arsenic trioxide (ATO) is a highly effective agent for the treatment of acute promyelocytic leukemia (APL). QT interval prolongation is common with ATO and can pose a barrier to effective administration. The objective of this study was to characterize the prevalence, management, and clinical consequences of QT prolongation in a large cohort of patients treated with ATO.
PATIENTS AND METHODS:
We analyzed 3,011 electrocardiograms from 113 patients with non-APL acute myeloid leukemia and myelodysplastic syndrome who were treated on a previously reported clinical trial. QT intervals were assessed using four different correction formulas, and data were correlated with clinical parameters and treatment with ATO.
RESULTS:
There were no clinically significant cardiac events in the study population. Of those receiving ATO therapy, 29 patients (26%) had rate-uncorrected QT values above 470 ms and 13 (12%) had values exceeding 500 ms. With the commonly used Bazett rate correction formula, 102 patients (90%) had QTc greater than 470 ms, including 74 (65%) above 500 ms. By using alternative rate correction formulas, only 24% to 32% of patients had rate-corrected QT intervals above 500 ms.
CONCLUSION:
QT interval prolongation is common with ATO treatment, but clinically significant arrhythmias are rare and can be avoided with appropriate precautions. Use of the Bazett correction may result in unnecessary interruptions in ATO therapy, and alternative rate correction formulas should be considered for routine electrocardiographic monitoring.
AuthorsGail J Roboz, Ellen K Ritchie, Rebecca F Carlin, Michael Samuel, Leanne Gale, Juliette L Provenzano-Gober, Tania J Curcio, Eric J Feldman, Paul D Kligfield
JournalJournal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 32 Issue 33 Pg. 3723-8 (Nov 20 2014) ISSN: 1527-7755 [Electronic] United States
PMID25245447 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2014 by American Society of Clinical Oncology.
Chemical References
  • Antineoplastic Agents
  • Arsenicals
  • Oxides
  • Arsenic Trioxide
Topics
  • Aged
  • Antineoplastic Agents (adverse effects)
  • Arsenic Trioxide
  • Arsenicals (adverse effects)
  • Electrocardiography (drug effects)
  • Female
  • Humans
  • Male
  • Middle Aged
  • Oxides (adverse effects)
  • Prevalence

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