Medline ® Abstracts for References 8,34
of 'Fluoropyrimidine-associated cardiotoxicity: Incidence, clinical manifestations, mechanisms, and management'
Fluoropyrimidine-associated cardiotoxicity: revisited.
Saif MW, Shah MM, Shah AR
Expert Opin Drug Saf. 2009;8(2):191.
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% ofpatients 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.
Yale University School of Medicine, FMP 116, CT 06520, New Haven, USA. firstname.lastname@example.org
Risk factors and prevention of cardiotoxicity induced by 5-fluorouracil or capecitabine.
Jensen SA, Sørensen JB
Cancer Chemother Pharmacol. 2006 Oct;58(4):487-93. Epub 2006 Jan 18.
AIM: 5-fluorouracil (5-FU) and its prodrug capecitabine are cardiotoxic. This retrospective study aimed to identify risk factors and to give practical measures to make such chemotherapy feasible if cardiotoxicity occur.
METHOD: Review of cardiotoxicity among 668 patients treated with 5-FU or capecitabine for gastrointestinal cancers.
RESULTS: Cardiotoxicity occurred in 29 cases (4.3%). The number of cases according to cardiotoxicity CTC grades 2-4 for patients with and without pre-existing cardiovascular disease were none, 10, and 2 cases, and 3, 14, and no cases, respectively (P=0.16). In three patients intercurrent decrease of renal clearances to<30, 48 and 71 ml min(-1) led to markedly increased cardiotoxicity. Chemotherapy dose reduction to 70 or 50%, either alone or in addition to antiangina medication prevented cardiotoxicity during subsequent chemotherapy in nine (60%) and three (20%) cases out of 15 assessable patients (P=0.001), respectively. To abolish symptoms of cardiotoxicity, sublingual nitroglycerine was efficient for 15 patients and inefficient for two (P=0.001).
CONCLUSION: Cardiac and renal co-morbidity are risk factors for 5-FU induced cardiotoxicity. In this situation, rechallenge with modified 5-FU-based chemotherapy regimen supported by symptomatic medical treatment is feasible.
Department of Oncology 5073, National University Hospital, 9 Blegdamsvej, 2100, Copenhagen, Denmark. email@example.com