Abstract
The cardiotoxicity of 5-fluorouracil (FU) was attributed to impurities present in the injected vials. One of these impurities was identified as fluoroacetaldehyde which is metabolised by isolated perfused rabbit hearts into fluoroacetate (FAC), a highly cardiotoxic compound. FAC was also detected in the urine of patients treated with FU. These impurities were found to be degradation products of FU that are formed in the basic medium employed to dissolve this compound. To avoid chemical degradation of this antineoplastic drug, the solution of FU that will be injected should be prepared immediately before use.
Highlights
5-fluorouracil (FU) is widely used alone or in combined protocols in the treatment of various malignancies including gastrointestinal, breast and head and neck cancer
In 281 patients receiving a continuous i.v. infusion of high doses of FU, cardiac events occurred in 26 patients (9.3%) and the lethality rate was 2.5%
Having at our disposal a powerful method for studying the metabolism of fluorinated drugs, especially fluoropyrimidines (Malet-Martino et al, 1990), we explored the possibility of a direct toxic effect of FU or one of its metabolites on the mycocardium using fluorine-19 nuclear magnetic resonance ('9F NMR) and the isolated perfused rabbbit heart (IPRH) model
Summary
5-fluorouracil (FU) is widely used alone or in combined protocols in the treatment of various malignancies including gastrointestinal, breast and head and neck cancer. The incidence of FU cardiotoxicity was reported to be 1.6% in a retrospective study of 1,083 patients receiving FU in various protocols (Labianca et al, 1982). Over the last decade, a number of retrospective or anecdotal reports have pointed to a higher incidence of FU-related complications in patients receiving high doses of FU. In 76 patients given cisplatin in combination with a continuous i.v. infusion of FU with regular clinical and ECG examination, Eskilsson et al (1988) observed adverse cardiac events (chest pain, arrythmia, ECG changes) in 14 patients (18%). In 281 patients receiving a continuous i.v. infusion of high doses of FU, cardiac events occurred in 26 patients (9.3%) and the lethality rate was 2.5% (de Forni et al, 1991)
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