Cartoon: multicenter prospective observational study of Cardiovascular Toxicity of Trifluridine/Tipiracil in metastatic colorectal cancer.

Background: Trifluridine/tipiracil (FTD/TPI), an oral fluoropyrimidine (FP) from the class of antimetabolites, approved for refractory metastatic colorectal cancer, is thought, to have no cardiac toxicity. The aim of this observational, prospective, multicenter study was to identify the incidence of cardiotoxicity of FTD/TPI; secondary objectives were to evaluate whether patients with previous heart diseases or cardiovascular risk factors, who were treated with FTD/TPI, were more susceptible to cardiotoxicity.

Materials And Methods: Patients received FTD/TPI according to clinical practice and provided informed consent to participate in this prospective study. Any symptoms that occurred during the treatment were reported by patients using a daily questionnaire (patient-reported outcome). In the case of symptoms suspected of cardiotoxicity patients were investigated with an ECG, enzymes, and a cardiology examination. Quality of life (QoL) was analyzed using a GF7 item of the FACT-G questionnaire. Univariate and multivariate logistic regression models were used to test associations between covariates and cardiotoxicity. Changes in QoL were evaluated during treatment.

Results: Four out of seventy-seven patients had cardiotoxicity ≥ G3 according to the common terminology criteria for adverse events during FTD/TPI treatment. There was: chest pain in 3 cases, and heart failure in one case. The overall incidence of cardiotoxicity was 5.19%. By univariate analysis, obesity, and anemia were demonstrated to be risk factors of cardiotoxicity, while with multivariate analysis, only hemoglobin levels were statistically associated with cardiotoxicity. Average QoL after treatment was not significantly decreased as compared to average basal QoL.

Conclusions: The risk of developing cardiotoxicity with FTD/TPI is lower than with other FP but it is not negligible. Previous heart diseases or cardiovascular risk factors do not represent an increased risk of cardiotoxicity of FTD/TPI. Further studies are needed to investigate this topic.