title: Incidence and risk factors for capecitabine-induced symptomatic cardiotoxicity: a retrospective study of 452 consecutive patients with metastatic breast cancer.
abstract: Case reports of capecitabine cardiotoxicity resemble those seen with intravenous 5-fluorouracil (5-FU) with chest pain as the predominant manifestation, but few studies of capecitabine cardiotoxicity are available. We aimed to determine the incidence of symptomatic cardiotoxicity from capecitabine in patients with breast cancer and to identify risk factors.
  
  
  
  We reviewed medical records of consecutive women with breast cancer treated with capecitabine (1000 mg/m2two times per day) from 2002 to 2012 at one institution.
  
  
  
  22 of 452 patients (4.9%) (95% CI 2.9% to 6.9%) had symptoms of cardiotoxicity (chest pain: n=13, dyspnoea: n=9, palpitations: n=2). 11 patients had changes on ECG (atrial fibrillation: n=5, ST deviations: n=3, T-wave abnormalities: n=2 and QTc prolongation: n=1). 2 patients (0.4%) sustained acute myocardial infarction. 1 patient (0.2%) developed cardiac arrest with lethal outcome. 4 of 6 patients (66%) retreated with capecitabine had recurrent symptoms at retreatment. Cardiac comorbidity (p=0.001), hypercholesterolaemia (p=0.005) and current smoking (p=0.023) were risk factors for cardiotoxicity in univariate analyses and remained significant when adjusted for age. Patients with cardiac comorbidity were 5.5 times (95% CI 2.0 to 14.8) more likely to develop cardiotoxicity. In the subgroup of patients with apparently no cardiac comorbidity, the incidence of cardiotoxicity was lower (3.7%) and hypercholesterolaemia (p=0.035) and current smoking (p=0.020) were risk factors of cardiotoxicity.
  
  
  
  The incidence of cardiotoxicity from capecitabine resembles that of intravenous 5-FU (≈5%). Cardiac comorbidity, hypercholesterolaemia and current smoking were associated with development of cardiotoxicity.
authors: Department of Oncology, Herlev and Gentofte Hospital, University of Copenhagen, Herlev, Denmark.|Department of Cardiology, Herlev and Gentofte Hospital, University of Copenhagen, Herlev, Denmark.
authors: Anne
authors: 0000-0003-2335-8219
authors: A
authors: Polk
authors: Department of Oncology, Herlev and Gentofte Hospital, University of Copenhagen, Herlev, Denmark.
authors: Nahid
authors: N
authors: Shahmarvand
authors: Department of Oncology, Herlev and Gentofte Hospital, University of Copenhagen, Herlev, Denmark.
authors: Kirsten
authors: K
authors: Vistisen
authors: Department of Cardiology, Herlev and Gentofte Hospital, University of Copenhagen, Herlev, Denmark.
authors: Merete
authors: M
authors: Vaage-Nilsen
authors: Department of Oncology, Herlev and Gentofte Hospital, University of Copenhagen, Herlev, Denmark.
authors: Finn Ole
authors: FO
authors: Larsen
authors: Department of Cardiology, Herlev and Gentofte Hospital, University of Copenhagen, Herlev, Denmark.
authors: Morten
authors: M
authors: Schou
authors: Department of Oncology, Herlev and Gentofte Hospital, University of Copenhagen, Herlev, Denmark.
authors: Dorte Lisbeth
authors: DL
authors: Nielsen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000453:epidemiology; D001943:Breast Neoplasms / Q000150:complications / Q000188:drug therapy*; D000069287:Capecitabine / Q000008:administration & dosage / Q000009:adverse effects*; D066126:Cardiotoxicity / Q000453:epidemiology* / Q000209:etiology*; D002637:Chest Pain / Q000139:chemically induced / Q000453:epidemiology / Q000503:physiopathology; D015897:Comorbidity; D003718:Denmark / Q000453:epidemiology; D005260:Female; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D009203:Myocardial Infarction / Q000139:chemically induced / Q000453:epidemiology; D009362:Neoplasm Metastasis / Q000188:drug therapy* / Q000517:prevention & control; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D000964:Antimetabolites, Antineoplastic; D000069287:Capecitabine
keywords: breast cancer; capecitabine; cardiotoxicity; chest pain; risk factors