Cardiotoxicity of 5-fluorouracil in combination with folinic acid in patients with gastrointestinal cancer

Abstract

Background. Cardiotoxicity related to the widely used cytotoxic compound 5‐fluorouracil (5‐FU) is rare compared with the frequency observed with the use of anthracyclines. More effective protocols incorporating active biomodulatory compounds like folinic acid (FA) or combination chemotherapy change type and severity of toxicity as well. The objective of the current study was to assess cardiotoxicity of the combination 5‐FU and folinic acid. Methods. The authors' multicenter experience with 390 patients treated for advanced gastrointestinal cancer with intermediate‐dose folinic acid and 5‐FU was reviewed. Results. The overall risk of cardiotoxicity was 3%, which is not significantly higher than that reported with 5‐FU alone. Eight of 53 patients with a history of cardiac disease reported cardiac symptoms (15.1%), compared with 5 of 337 patients (1.5%) with a no history of cardiac disease. Median time to symptoms was 3 days (range, 2–6). Nine patients had symptoms resembling myocardial ischemia, one patient died due to assumed myocardial infarction related closely to fluorouracil treatment, four patients had supraventricular arrhythmia, and one patient had congestive heart failure. A history of cardiac disease was the only risk factor associated with cardiotoxicity. Relapses were frequent on reinstitution of therapy despite cardiac symptoms in the preceding cycle. Therapeutically or prophylactically administered nitrates had no significant effect. Conclusion. Physicians should be aware of the cardiotoxic properties of active fluorouracil treatment. The combination of 5‐FU and leucovorin does not differ from single‐agent therapy in frequency or type of cardiotoxicity. Close monitoring of patients is mandatory, especially for those patients at high risk for cardiac side effects. Treatment should be discontinued if coronary symptoms develop, because neither effective treatment nor prophylaxis exists for such symptoms.

Drug-Induced Cardiomyopathies

“…A direct interference of 5-fluorouracil with the myocardial cell metabolism leading to cellular hypoxia has been suggested from a study with an isolated perfused rat heart model (Millart et al 1992). In addition, cases of dilated cardiomyopathy and congestive heart failure have been reported after 5-fluorouracil treatment, also suggesting a direct toxic effect on the myocardium (Schöber et al 1993;Weidmann et al 1995). Capecitabine may cause ischaemia and cytarabine may cause pericarditis (Wu 2008).…”

Coronary Vasospasm Secondary to 5-Fluorouracil and Its Management: Case Report

“…sional 5-FU may lead to cardiotoxicity that presents with angina, elevated cardiac enzymes and electrocardiogram (ECG) changes at various dose levels [3,4]. Cardiotoxicity has been reported to occur with 5-FU administered either as a single agent or in combination with other chemotherapy agents [4].…”

“…Cardiotoxicity has been reported to occur with 5-FU administered either as a single agent or in combination with other chemotherapy agents [4].…”

“…The incidence of 5-FU cardiotoxicity ranged from 1.6% to 8.5% in subsequent reports [3,4]. Coronary vasospasm secondary to 5-FU is one of the rare, but life-threatening, forms of cardiotoxicity, which should be kept in mind throughout delivery of CT.…”

“…The most prominent doselimiting manifestations include myelosuppression, diarrhea and hand-foot syndrome. Although it is rare, 5-FU may also lead to cardiotoxicity that presents with angina, elevated cardiac enzymes and electrocardiogram (ECG) changes [3,4].…”