Cardiotoxicity of the antiproliferative compound fluorouracil

The antimetabolite fluorouracil (5-FU) is frequently administered for chemo therapy of various malignant neoplasms. The drug is well known for its adve rse effects involving bone marrow, skin, mucous membranes, intestinal tract and central nervous system, whereas its cardiotoxicity is less familiar to clinicians, The pathophysiology of fluorouracil-associated cardiac adverse events is co ntroversial and conclusions are based on clinical studies and case reports more than on solid experimental evidence. While clinical and electrocardiog raphic features suggest myocardial ischaemia as a main aetiological factor, possibly induced by coronary vasospasm, histomorphological and biochemical studies indicate a more direct drug-mediated cytotoxic action. Estimates o f the overall incidence of fluorouracil cardiotoxicity have varied widely f rom 1.2 to 18% of patients. Patients may present with angina-like chest pai n, cardiac arrhythmias or myocardial infarction, There is no unequivocally effective prophylaxis or treatment in this syndrome. Once fluorouracil admi nistration is discontinued symptoms are usually reversible, although fatal events have been described, The overall mortality rate has been estimated t o be between 2.2 and 13.3%. There is a high risk of relapse when patients a re re-exposed to this drug following previous cardiac incidents. From the present data it is concluded that cardiotoxicity is a relevant but underestimated problem in fluorouracil treatment, Since the mechanisms of fluorouracil-associated cardiotoxicity an not yet fully understood, all pat ients undergoing this chemotherapy have to be carefully evaluated and monit ored for cardiac risk factors and complaints. After cardiotoxic events, flu orouracil should definitely be withdrawn and replaced by an alternative ant iproliferative regimen.