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The Cardiotoxic Potential of the 5-HT₃ Receptor Antagonist Antiemetics: Is There Cause for Concern?

Memorial Sloan-Kettering Cancer Center, New York, New York, USA

Correspondence: Deborah L. Keefe, M.D., M.PH., Cardiology and Critical Care Services, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021, USA. Current address: P.O. Box 500, New Rochelle, New York 10804-0500, USA. e-mail: dkclinpharm{at}aol.com

Purpose. To review and evaluate the potential cardiac effects of 5-HT₃ antiemetic treatment in patients who may be predisposed to cardiac complications resulting from malignancy, cytotoxic oncologic regimens, or preexisting comorbid conditions.

Design. A literature review was conducted on the negative cardiovascular effects of chemotherapeutic agents, and, more specifically, on the cardiac interactions of the 5-HT₃ receptor antagonists commonly used to treat chemotherapy-induced nausea and vomiting.

Results. Clinical studies in healthy subjects have reported electrocardiograph changes following administration of 5-HT₃ receptor antagonists. However, there are limited data on the use of 5-HT₃ antiemetics when administered with cardiotoxic chemotherapy. Nonetheless, the development of significant electrocardiograph changes with some agents may indicate a potential for significant cardiac effects in patients, particularly those who may be predisposed to cardiac complication.

Conclusions. As the predicted human life span increases, clinicians will be treating a larger, older oncology population. Because two of the most common major comorbidities are cardiovascular related, we need to be acutely aware of the toxic effects of chemotherapy, as well as the possible cardiac interaction of supportive agents, specifically the 5-HT₃ antiemetics. Until more data are made available, the best antiemetic option for patients receiving emetogenic and cardiotoxic chemotherapy may be the agent with the fewest apparent cardiac effects.

Key Words. Cardiotoxicity • 5-HT₃ antiemetics • Granisetron • Ondansetron • Dolasetron

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