Abstract Body (Do not enter title and authors here): Background: Cardiovascular toxicity is a common complication of fluoropyrimidine therapy, with angina from coronary vasospasm being the most frequent adverse effect. Despite its prevalence, risk factors and management strategies remain poorly defined, leading to inconsistent clinical approaches among different institutions. This study aims to characterize the clinical features, management, and outcomes of patients who developed fluoropyrimidine-induced angina at the Cleveland Clinic.

Methods: We conducted a retrospective, single-center study of patients who developed angina during fluoropyrimidine therapy between 2017 and 2023. Patients with clear non-cardiac chest pain were excluded. Clinical presentation, management strategies, and treatment outcomes were collected. Logistic regression was used to identify predictors of chest pain recurrence among patients who were re-challenged following first angina.

Results: A total of 137 patients were included. Mean age was 62.4 years, and 50.4% were male. The majority had colorectal cancer (54%). Among those, 61.3% received IV 5-fluorouracil, while 38.7% received oral capecitabine. Most events occurred during the first four treatment cycles (75.2%). At presentation, 43.3% had new ischemic changes on electrocardiogram, and 39% of those who underwent echocardiography had new abnormalities. Left heart catheterization was performed in 24.1% of cases, with most revealing normal or only mild coronary artery disease. Fluoropyrimidine therapy was discontinued in 35.9% of patients, while 64.1% were re-challenged. Among re-challenged patients, 35.7% experienced recurrence of chest pain. No clinical, oncologic, or treatment-related variables were significantly associated with recurrence.

Conclusion: This study highlights our experience in managing fluoropyrimidine-induced angina. While re-challenge is frequently pursued, recurrence of chest pain remains common and unpredictable, with no clear clinical or treatment-related predictors identified. These findings highlight the need for better risk stratification and standardized management strategies in a common toxicity in a high-risk population.