At present, the various mechanisms involved in 5-fluorouracil (5-FU)-correlated cardiotoxicity remain to be elucidated and a universally accepted prophylaxis or treatment for this specific toxicity is not available. Although it may improve time to progression, survival and clinical benefit, a 5-FU-based regimen usually has to be discontinued if a patient experiences cardiotoxicity. Here, we describe our experience with three cases of 5-FU-associated cardiotoxicity. The angina-like pain that appeared approximately 95 h after beginning 5-FU therapy was apparently independent of the drug's administration modality. In the two patients receiving 5-FU 12-h flat continuous infusion from 22.00 to 10.00 h (5-FU 12-h c.i.) in combination with other drugs, the dose of 5-FU was reduced by 10 -20% and patients received prophylactic transepidermal nitroglycerin. In the third patient, 5-FU administration modality was changed and prophylactic therapy was not given. By taking these precautions, the patients no longer complained of anginal pain and none of them discontinued chemotherapy. (Kohne et al, 1998). The spectrum of toxicities associated with 5-FU involves the gastrointestinal tract, the bone marrow, the skin and the central nervous system. Last, but not the least, 5-FU may give cardiac toxicity that is less familiar to physicians and this may present as precordial pain, atrial arrhythmias, electrocardiogram (EKG) ST-T wave changes, ventricular dysfunction and cardiogenic shock.The overall incidence of 5-FU cardiotoxicity varies from 1.2 to 18% of patients and is usually underestimated, since silent EKG alterations often occur (Klaus Becker et al, 1999). The different mechanisms involved in 5-FU-associated cardiotoxicity are not yet fully understood and no unequivocally effective prophylaxis or treatment for this specific toxicity exists. Here, we describe three cases of 5-FU-associated cardiotoxicity, its clinical management and the prophylactic treatment used.
PATIENTS AND METHODS
Case 1A 57-year-old male, with positive family history for acute myocardial infarction (AMI) but with no history of cardiovascular disease, came to our observation after undergoing an anterior resection of the rectum for a stage III rectal -sigmoid adenocarcinoma (RSA) ( Table 1). Physical examination, chest X-rays, blood pressure and EKG were all within normal limits. The patient received four cycles of adjuvant chemotherapy with 5-FU (370 mg m À2 day À1 ) and folinic acid (FA) (50 mg tot À1 ) i.v. for 5 days, every 3 weeks.During adjuvant chemotherapy, disease progressed with liver metastasis and the patient's therapy was changed to irinotecan (180 mg m À2 ) day 1 and 5-Fu 12-h flat continuous infusion from 22.00 to 10.00 h (5-FU 12-h c.i.) (900 mg m À2 day À1 ) for 4 days, every 2 weeks. Approximately 93 h after starting the first cycle of the second 5-FU regimen, the patient presented angina-like pain that lasted a few minutes and disappeared with oral nitroglycerin. The blood pressure was 160/115 mmHg and the heart rate was 105 beats min...
