Managing 5FU Cardiotoxicity in Colorectal Cancer Treatment

Abstract

Fluorouracil (5FU) is the backbone chemotherapy agent in the treatment of colorectal cancer (CRC). Cardiotoxicity represents an uncommon but serious side effect of treatment with 5FU. Here, we review the current literature on 5FU-cardiotoxicity in the setting of CRC specifically, with a focus on data from the modern era of combination chemotherapy. Despite decades of study, there is little consensus on risk factors and biomarkers for 5FU-cardiotoxicity, nor how patients with CRC should be managed following a cardiotoxicity event. Given the elevated risk of recurrent cardiotoxicity on rechallenge, the use of alternative regimens that do not contain 5FU is a critical aspect of management. Data on the cardiotoxicity risk and efficacy of non-5FU regimens in CRC are therefore reviewed in detail.

Acute, Prolonged, and Extensive Myocardial Ischemia in a Patient With Colorectal Cancer

“…Based on this early clinical evolution, the colorectal cancer chemoadjuvant therapy was reassessed due to the known capability of fluorouracil and its derivative capecitabine to induce coronary spasm. 1,2 Treatment with capecitabine had been initiated just 3 days before and was likely associated with the extensive ischemic ECG signs of transmural ischemia that were observed at the initial presentation, which was in all likelihood due to an occlusive vasoconstriction of the left anterior descending coronary artery before the origin of the first diagonal branch.…”

“…Anginal pain is the most common cardiac toxic effect, with an incidence between 1.2% and 4.3% of treated patients. 2,4 The mechanism is supposed to be multifactorial, with coronary vasospasm accredited as the most important one. 5 This iatrogenic cause should be considered whenever a patient with recent onset of therapy presents with acute transmural ischemia to administer nitrates and avoid powerful antithrombotics that may cause severe bleeding in these patients.…”

Rechallenging Fluoropyrimidine-Induced Cardiotoxicity and Neurotoxicity: A Report of Two Cases

“…Cardioprotective regimen was given the day before starting 5-FU infusion/oral capecitabine and continued until completion of infusion/treatment [ 9 ]. Rechallenge should be performed in a vigilantly monitored setting if no alternatives are available [ 10 ]. Dose reduction of FPs, transitioning to a bolus form 5-FU, and prophylactically treating with nitrates or CCBs are the key components while rechallenging patients with FPs after the initial cardiac event [ 11 ].…”

Coronary atherosclerosis and chemotherapy: From bench to bedside

“…Experimental evidence also supports the direct toxic effects of 5-FU on the coronary endothelium. Anaka and Abdel-Rahman ( 89 ) used electron microscopy to observe the endothelial cells of rabbit arterioles after 5-FU treatment. They studied the local and systemic effects of 5-FU on the endothelial cells of rabbits at 1, 3, 7, 14, and 30 days after 5-FU treatment.…”

“…They studied the local and systemic effects of 5-FU on the endothelial cells of rabbits at 1, 3, 7, 14, and 30 days after 5-FU treatment. Severe cell damage associated with thrombosis was found ( 89 ). Clinical trial evidence also supports the direct toxic effects of 5-FU on the coronary endothelium and the hypercoagulable state, which together induce acute thrombotic events ( 54 ).…”