title: Incidence of capecitabine-related cardiotoxicity in different treatment schedules of metastatic colorectal cancer: A retrospective analysis of the CAIRO studies of the Dutch Colorectal Cancer Group.
abstract: The frequency of capecitabine-related cardiotoxicity has been reported to be low but includes serious adverse events. We conducted a retrospective analysis of the incidence and severity of capecitabine-related cardiotoxicity in different regimens in the treatment of metastatic colorectal cancer in three randomised phase 3 studies.
  
  
  
  We used data of cardiac events reported in the CAIRO, CAIRO2 and CAIRO3 studies of the Dutch Colorectal Cancer Group (DCCG) and analysed the incidence and severity of cardiac events in the different treatment regimens of the trials which all included the use of capecitabine. The following events were included: chest pain, newly diagnosed cardiac ischaemia/infarction, atrial fibrillation, other arrhythmias and heart failure, all graded according to National Cancer Institute Common Toxicity Criteria (NCI-CTC).
  
  
  
  A total of 1973 patients were included, who received a total of 2461 capecitabine-based lines of treatment. Overall, 5.9% of patients (n = 117) experienced at least one cardiac event, and 2.3% (n = 46) experienced at least one grade ≥3 event. Three patients had two cardiac events. The most frequently observed cardiac event was ischaemia/infarction (2.9%, n = 57), followed by arrhythmias (2.0%, n = 40, including atrial fibrillation in 10 patients), chest pain (0.8%, n = 16) and heart failure (0.4%, n = 7). The highest incidence of cardiac events was observed in patients treated with capecitabine in combination with oxaliplatin and bevacizumab (12%, n = 43).
  
  
  
  We observed capecitabine-related cardiotoxicity in 5.9% of patients, and severe cardiotoxicity in 2.3% of patients. Combination treatment with capecitabine, oxaliplatin and bevacizumab was associated with the highest risk of cardiotoxicity.
authors.affiliation: Department of Medical Oncology, Academic Medical Center, University of Amsterdam, Mijbergdreef 9, 1105 AZ Amsterdam, The Netherlands. Electronic address: j.j.kwakman@amc.uva.nl.
authors.forename: Johannes J M
authors.initials: JJ
authors.lastname: Kwakman
authors.affiliation: Department of Medical Oncology, Máxima Medical Center, Ds. Th. Fliednerstraat 1, 5631 BM Eindhoven, The Netherlands. Electronic address: lieke.simkens@mmc.nl.
authors.forename: Lieke H J
authors.initials: LH
authors.lastname: Simkens
authors.affiliation: Department of Data Management, Netherlands Comprehensive Cancer Center (IKNL), Hatertseweg 1, 6533 AA Nijmegen, The Netherlands. Electronic address: l.mol@iknl.nl.
authors.forename: Linda
authors.initials: L
authors.lastname: Mol
authors.affiliation: Department of Cardiology, Academic Medical Center, University of Amsterdam, Mijbergdreef 9, 1105 AZ Amsterdam, The Netherlands. Electronic address: w.e.kok@amc.uva.nl.
authors.forename: Wouter E M
authors.initials: WE
authors.lastname: Kok
authors.affiliation: Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. Electronic address: m.koopman-6@umcutrecht.nl.
authors.forename: Miriam
authors.initials: M
authors.lastname: Koopman
authors.affiliation: Department of Medical Oncology, Academic Medical Center, University of Amsterdam, Mijbergdreef 9, 1105 AZ Amsterdam, The Netherlands. Electronic address: c.punt@amc.uva.nl.
authors.forename: Cornelis J A
authors.initials: CJ
authors.lastname: Punt
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000453:epidemiology; D000068258:Bevacizumab / Q000008:administration & dosage; D000069287:Capecitabine / Q000008:administration & dosage / Q000009:adverse effects; D002277:Carcinoma / Q000188:drug therapy* / Q000556:secondary; D066126:Cardiotoxicity; D002637:Chest Pain / Q000139:chemically induced / Q000453:epidemiology; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006333:Heart Failure / Q000139:chemically induced* / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D009203:Myocardial Infarction / Q000139:chemically induced* / Q000453:epidemiology; D017202:Myocardial Ischemia / Q000139:chemically induced / Q000453:epidemiology; D009362:Neoplasm Metastasis; D009426:Netherlands / Q000453:epidemiology; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies
chemical_list: D000964:Antimetabolites, Antineoplastic; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000068258:Bevacizumab; D000069287:Capecitabine
keywords: Capecitabine; Cardiotoxicity; Retrospective analysis