Fluoropyrimidine-Induced Cardiotoxicity: Manifestations, Mechanisms, and Management.
Fluoropyrimidines-5-fluorouracil (5-FU) and capecitabine-have been implicated as cardiotoxic chemotherapy agents. This rare, albeit potentially serious toxicity has been described in nearly four decades of case reports, case series, and in vitro modeling; however, there is a paucity in clinical trials and prospective analyses focused on cardioprotective strategies and cardiotoxic surveillance of these agents. While much attention has focused on the well-known cardiac toxicity of anthracyclines and monoclonal antibody agents such as trastuzumab, fluoropyrimidines remain one of the most common causes of chemotherapy-associated cardiotoxicity. The introduction of capecitabine, an oral prodrug of 5-FU, has made the treatment of solid tumors more convenient along with a subsequent rise in documented cardiotoxic cases. This review discusses the symptomatology, clinical manifestations, and proposed molecular mechanisms that attempt to describe the heterogeneous spectrum of fluoropyrimidine-induced cardiotoxicity. Four case examples showcasing the varied manifestations of cardiotoxicity are presented. Finally, several proposed management strategies for cardiotoxicity and post-hospital course precautions are discussed.
Department of Medicine, UCLA Medical Center, University of California at Los Angeles, Los Angeles, CA, USA.
Michael E
ME
Layoun
Division of Cardiology, Department of Medicine, UCLA Medical Center, University of California at Los Angeles, Los Angeles, CA, USA.
Chanaka D
CD
Wickramasinghe
Division of Internal Medicine, Department of Medicine, Beaumont Hospital-Dearborn, Dearborn, MI, USA.
Maria V
MV
Peralta
Division of Cardiology, Department of Medicine, UCLA Medical Center, University of California at Los Angeles, Los Angeles, CA, USA. ehyang@mednet.ucla.edu.
Eric H
EH
Yang
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D066126:Cardiotoxicity / Q000209:etiology* / Q000517:prevention & control*; D054715:Cardiotoxins / Q000009:adverse effects*; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000517:prevention & control; D019468:Disease Management; D006801:Humans; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy*; D011743:Pyrimidines / Q000009:adverse effects*
D000970:Antineoplastic Agents; D054715:Cardiotoxins; D011743:Pyrimidines
5-Fluorouracil; Acute coronary syndrome; Arrhythmia; Capecitabine; Cardiotoxicity; Chest pain; Coronary artery disease; Coronary vasospasm; Fluoropyrimidine