Retrospective cohort study of outcomes and safety of chemotherapy reintroduction after fluoropyrimidine-induced cardiotoxicity

Fluoropyrimidines are widely used in the treatment of various cancers, despite their well-documented risk of cardiotoxicity. A retrospective study at the Hospices Civils de Lyon (France) characterized cardiovascular events associated with fluoropyrimidine use, evaluated their management, and investigated the prognostic impact of chemotherapy reintroduction. Among 141 patients admitted for cardiovascular events between 2014 and 2024 who received fluoropyrimidine chemotherapy within the preceding year, the most frequent cardiovascular events were cornoary artery disease (30.5%), atrial fibrillation (28.4%), and heart failure (19.9%). Post-event, three primary therapeutic strategies were implemented in the follow-up cohort (n=114): fluoropyrimidine reintroduction (n=53; 38.3%), switch to alternative chemotherapy (n=25; 17.7%), and transition to palliative care (n=36; 25.5%). Recurrent cardiotoxicity after reintroduction occurred in eight patients (14.8%), with only one recurrent coronary event. At 2-year follow-up, overall survival tended to be higher in the reintroduction group compared to switching to alternative chemotherapy (HR 1.77; p=0.088) and compared to palliative care (HR 8.31; p<0.001). No significant increase un unplanned hospitalizations was observed in the reintroduction group compared to the alternative chemotherapy group. The authors conclude that these findings suggest that fluoropyrimidine reintroduction appears to have a favorable benefit/risk balance for selected patients.