FLUOROURACIL (FU) CARDIOTOXICITY (CDT) AND COAGULATION PARAMETERS

FU CDT is a syndrome with diverse aspects and obscure pathogenesis. It is more frequent withshort-term infusional regimens. A course of FU, 1 gr/m2/d c.i. for 5 days, was administered to 20 patients (pts) with advanced head and neck or gastrointestinal cancers prior to conventional therapy. Blood pressure, pulse and EGG were recorded before treatment and every 4-6 hours during chemotherapy (CT). Plasma and serum samples were obtained at 0., 24. and 120. hours, and levels of creatinine phosphokinase-myocardial band, fibrinogen, fibrinopeptid A, protein C, protein S, and antithrombin III were measured. Ten pts with early stage malignancy and no liver involvement were used as controls for baseline levels. During CT, a 41 year-old male patient developed chest pain and ECG findings suggesting anterolateral myocardial infarction, but cardiac ezymes remained normal. Nine pts displayed ECG changes during the FU infusion; namely ischemic ST segment and T wave abnormalities, QT prolongation, frequent ventricular and supraventricular ectopic beats, and alternating voltage. Heart rate, PR segment, QRS wave and Qtc segment were measured in serial ECG recordings. During the FU infusion, the QRS wave showed significant widening which still remained within the physiological limits. Significant and pathologic prolongation of the corrected QT (Qtc) was noted. There was no significant change in any of the coagulation parameters tested. The frequency of symptomatic CDT in this study (5%) is in accordance with previous reports, but the high frequency of asymptomatic ECG changes (45%) approaches those reported with holter monitoring. Electrophysiologic findings such as QRS widening and Qtc prolongation reveal another aspect of FU CDT. The role of these findings in explaining the arhythmias, ventricular fibrillation and sudden death occuring during FU infusion, and the significance of Qtc prolongation in predicting CDT remain to be determined in large trials.