IV. 5-FLUOROURACIL
This is a frequently used agent and its associated cardio-toxicity may be more common than previously thought.
Cardiotoxic effects occur when the drug is administered as a continuous infusion and within 5 h of infusion. Symptoms and signs are usually reversible within a few days. 5-Fluorouracil should be discontinued when cardiotoxicity arises and reinstitution is not advisable due to high incidence of recurrence. The overall incidence of cardiotoxicity ranges from 2 to 18% with a mortality of 2–15%. Unfortunately, there is no method to predict which patients are risk, because it has been noted that pre-existing heart disease, dose and route of administra¬tion, age, and chest radiation do not consistently correlate with associated toxicity. In a study of 1083 patients, however, those with a prior history of heart disease had a significantly increased risk (4.5 vs. 1.1%) of developing chest pain compared with patients without known heart disease (<0.01).
A. Acute Cardiovascular Effects
Chest pain often may not have a cardiac origin, but true anginal pain has been noted with the use of 5-fluorouracil, albeit rarely. Onset of pain usually occurs within hours of receiving a second or third dose but may be associated with the first dose. Anginal attacks may occur upon rechal-lenge with fluorouracil and, unfortunately, may not be prevented with the usual antianginal medications that include nitrates or calcium antagonists. In some patients typical crushing chest pain may occur with electrocardio-graphic changes that improve after discontinuation of the drug. Patients who have experienced chest discomfort with ECG changes should be administered further doses of 5-fluorouracil only if absolutely necessary, and this should be done in a cardiac unit with appropriate monitoring. The ECG may reveal no abnormalities during chest pain, yet several hours later ST segment elevation or nonspecific ST-T wave changes may be observed. Myocardial infarc¬tion, cardiogenic shock, and death have been reported, albeit rarely.