Fluoropyrimidine‑induced cardiotoxicity in colorectal cancer patients: a prospective observational trial (CHECKPOINT)

Lombardi,Pasquale; Aimar,Giacomo; Peraldo-Neia,Caterina; Bonzano,Alessandro; Depetris,Ilaria; Fenocchio,Elisabetta; Filippi,Roberto; Quarà,Virginia; Milanesio,Michela; Cavalloni,Giuliana; Gammaitoni,Loretta; Basiricò,Marco; Cagnazzo,Celeste; Ostano,Paola; Chiorino,Giovanna; Aglietta,Massimo; Leone,Francesco

doi:10.3892/or.2022.8468

Fluoropyrimidine‑induced cardiotoxicity in colorectal cancer patients: a prospective observational trial (CHECKPOINT)

Authors:
- Pasquale Lombardi
- Giacomo Aimar
- Caterina Peraldo-Neia
- Alessandro Bonzano
- Ilaria Depetris
- Elisabetta Fenocchio
- Roberto Filippi
- Virginia Quarà
- Michela Milanesio
- Giuliana Cavalloni
- Loretta Gammaitoni
- Marco Basiricò
- Celeste Cagnazzo
- Paola Ostano
- Giovanna Chiorino
- Massimo Aglietta
- Francesco Leone
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Affiliations: Department of Oncology, University of Turin, I-10124 Torino, Italy, Laboratory of Cancer Genomics, Fondazione Edo ed Elvo Tempia, I-13900 Biella, Italy, Candiolo Cancer Institute, FPO‑IRCCS, I-10060 Candiolo, Italy, Division of Medical Oncology 1, AOU City of Health and Science of Turin, I-12126 Turin, Italy, Department of Medical Oncology, Candiolo Cancer Institute, FPO‑IRCCS, I-10060 Candiolo, Italy, Department of Public Health and Pediatric Sciences, AOU City of Health and Science of Turin, Regina Margherita Hospital, I-10126 Torino, Italy, Department of Medical Oncology, Infermi Hospital of Biella, Ponderano, I-13875 Biella, Italy
Published online on: December 21, 2022 https://doi.org/10.3892/or.2022.8468
Article Number: 31
Copyright: © Lombardi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Fluoropyrimidines (FP) are the backbone chemotherapy in colorectal cancer (CRC) treatment; however, their use is associated with cardiotoxicity, which is underreported. In the present study, it was aimed to prospectively determine the incidence rates and related risk factors of FP‑induced cardiotoxicity (FIC) in CRC patients and at identifying predictive biomarkers. A total of 129 consecutive previously untreated CRC patients underwent active cardiological monitoring, including 5‑items simplified questionnaire on symptoms, electrocardiogram (ECG) and plasma sample collection during FP chemotherapy. FIC was defined as the presence of ECG alterations and/or the arising of at least one symptom of chest pain, dyspnoea, palpitations or syncope. The primary objective was the evaluation of FIC incidence. Secondary objectives were the correlation of FIC with well‑known cardiological risk factors and the identification of circulating biomarkers (serum levels of troponin I, pro hormone BNP; miRNA analysis) as predictors of FIC. A total of 20 out of 129 (15.5%) patients experienced FIC. The most common symptoms were dyspnoea (60%) and chest pain (40%), while only 15% of patients presented ECG alterations, including one acute myocardial infarction. Retreatment with FP was attempted in 90% of patients with a favourable outcome. Despite 48% of patients having cardiological comorbidities, an increased FIC was not observed in this subgroup. Only the subgroup of females with the habit of alcohol consumption showed an increased risk of FIC. None of the circulating biomarkers evaluated demonstrated a clinical utility as FIC predictors. FIC can be an unexpected, life‑threatening adverse event that can limit the subsequent treatment choices in patients with CRC. In this prospective study, well‑known cardiological comorbidities were not related to higher FIC risk and circulating biomarkers predictive of toxicity could not be found. With careful monitoring, mainly based on symptoms, almost all patients completed the FP treatment.

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