5-fluorouracil exposure resulted in cardiotoxicity presenting commonly as angina (45%) or myocardial infarction (22%), with an 8% mortality rate that increased to 13% upon reexposure.
5-fluorouracil cardiotoxicity is a significant clinical phenomenon that frequently presents as angina or myocardial infarction early in the treatment course, is independent of dose, and carries a notable risk of mortality, particularly upon rechallenge.
BACKGROUND: The syndrome of 5-fluorouracil (5-FU)-associated cardiotoxicity remains poorly defined. PATIENTS AND METHODS: We performed a literature review (1969 - 2007) and compiled data derived from 377 evaluable cases out of 448 reported cases. RESULTS: Patient age ranged from 14 to 86 years. Of the patients 65% were 55 years old and the male:female ratio was 1.5:1. The most commonly treated tumors were gastrointestinal (60%), head and neck (22%) and breast (4%). Of the patients 14% had a history of heart disease whereas cardiac risk factors were found in 37%. Mode of administration included: continuous infusion (72%); bolus (22.5%); intermediate infusion (3%); oral (2%); and intraperitoneal (1 patient). The dosages of 5-FU used were < 750 mg/m(2)/day (36%), 751 - 999 (16%), 1,000 (26%), 1,001 - 1,499 (4%) and 1,500 (16%). Of the patients 54% received 5-FU in combination with other chemotherapeutic agents (cisplatin 44%) whereas 51% received 5-FU alone or with leucovorin. Only 4% patients had undergone previous or concomitant radiation therapy to the mediastinum. Of cardiac incidents that happened 69% were seen during or within 72 h of the first cycle of 5-FU. Angina occurred in 45% of patients whereas myocardial infarction was seen in 22%, arrhythmias in 23, acute pulmonary edema in 5, cardiac arrest and pericarditis in 1.4 and heart failure in 2. Electro-cardiographic evidence of ischemia or ST-T changes were recorded in 69% of patients, but abnormal cardiac enzymes were found in only 12%. The cardiac symptoms were reproducible in 47%, including in one patient subsequently treated with 5-FU p.o. Symptoms were also elicited when the same patients were treated with lower doses or different schedules. Of the patients 68% responded to conservative anti-anginal therapy, although prophylactic coronary vasodilators had limited efficacy. Overall, 8% of patients showing cardiotoxicity on 5-FU administration died. Furthermore, 13% reexposed to 5-FU died. CONCLUSIONS: Our review suggests that 5-FU cardiotoxicity is an infrequent but real phenomenon that is independent of dose and may be related to a continuous infusion schedule. The presence of cardiac risk factors is not predictive. Patients should be observed closely and 5-FU administration discontinued if cardiac symptoms develop. A rechallenge with 5-FU should be reserved only for those patients in whom there is no reasonable alternative therapy and should be performed in the setting of aggressive prophylaxis and close monitoring.
Saif et al. (2009) conducted a review in 5-fluorouracil (5-FU)-associated cardiotoxicity (n=377). 5-fluorouracil (5-FU) was evaluated on Cardiotoxicity symptoms and mortality. 5-fluorouracil exposure resulted in cardiotoxicity presenting commonly as angina (45%) or myocardial infarction (22%), with an 8% mortality rate that increased to 13% upon reexposure.