Medline ® Abstracts for References 5,15,34,35
of 'Fluoropyrimidine-associated cardiotoxicity: Incidence, clinical manifestations, mechanisms, and management'
Cardiac toxicity of 5-fluorouracil: a study on 1083 patients.
Labianca R, Beretta G, Clerici M, Fraschini P, Luporini G
The possible onset of cardiotoxic manifestations during chemotherapy with 5-fluorouracil (5-FU) was evaluated in 1083 patients treated with the drug for various kinds of neoplasm. We recognized 17 cases of 5-FU cardiopathy (usually anginous crises but also myocardial infarction). The comprehensive incidence was 1.6%, with a significantly greater risk (4.5% vs 1.1%) for patients with a positive anamnesis of previous cardiopathy. On the contrary, age and combination with other antiblastic drugs had no affect on the appearance of cardiopathy. We conclude that 5-FU cardiopathy, although rare, has to be taken into account in oncologic practice, chiefly in those patients already affected with cardiac diseases.
Symptomatic cardiotoxicity associated with 5-fluorouracil.
Meyer CC, Calis KA, Burke LB, Walawander CA, Grasela TH
Pharmacotherapy. 1997 Jul-Aug;17(4):729-36.
A prospective cohort study was conducted in 35 hospitals with oncology units to determine the incidence of symptomatic cardiotoxicity in patients receiving continuous infusions of 5-fluorouracil (5-FU), and to identify risk factors that could contribute to the development of 5-FU-associated cardiotoxicity. A sample of 483 patients [197 (41%) women, overall average age +/- SD 60.9 +/- 11.9 yrs]were followed for one cycle of 5-FU infusion. Thirty-eight (7.9%) patients had abrupt termination of the infusion. There were 9 (1.9%) cases of suspected or documented cardiotoxic events. Cardiotoxicity occurred in 7 (3.35%) of 209 patients receiving their first course of 5-FU and in 2 (0.73%) other patients (p=0.044). Based on univariate analysis, the following patient groups were at elevated risk of cardiotoxicity: those with preexisting cardiac disease (RR=6.83, p=0.0023); patients receiving calcium channel blockers (RR=4.75, p=0.014); those receiving nitrates (RR=9.18, p=0.007); and patients receiving concomitant etoposide (RR=10.32, p=0.022). Patients with underlying cardiac disease require close monitoring while receiving continuous infusions of 5-FU. They should be observed for signs and symptoms of cardiotoxicity, and vital signs should be measured frequently. Continued reporting of 5-FU-associated cardiotoxicity is necessary to identify other patients at risk.
Drug Information Center, Division of Pharmacy Practice, University of Missouri-Kansas City, USA.
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
Evaluation of cardiotoxicity of a combined bolus plus infusional 5-fluorouracil/folinic acid treatment by echocardiography, plasma troponin I level, QT interval and dispersion in patients with gastrointestinal system cancers.
Oztop I, Gencer M, Okan T, Yaren A, Altekin E, Turker S, Yilmaz U
Jpn J Clin Oncol. 2004 May;34(5):262-8.
OBJECTIVE: To evaluate the cardiotoxicity of LV5FU2 regimen (bolus plus infusional 5-fluorouracil/folinic acid) treatment by non-invasive methods such as echocardiography, plasma troponin I (TnI) level, QT interval and QT dispersion on ECG.
METHODS: Twenty-two patients with gastrointestinal cancer who received LV5FU2 chemotherapy were evaluated prospectively during 12 cycles of chemotherapy. Plasma TnI assay and ECG recording analyses were performed before the first cycle, at 24 h, before each cycle until cycle 6 and every three cycles thereafter. The longest QT interval measurement on each recording corrected with Bazzett's formula was considered as QTmax and the difference between the QTmax and the shortest corrected QT interval was considered as QT dispersion (QTd). A complete M-mode, 2D and color Doppler echocardiogram was performed at baseline and at the first, third and sixth months of treatment.
RESULTS: Echocardiography did not show any significant change in either systolic or diastolic functions. Also, TnI measurements were found to be below detectable level in all patients and in all measurements. Meanwhile, significant prolongations of QTmax and QTd were observed as early as 24 h after first administration of chemotherapy. These events persisted and became more important over the duration of chemotherapy (P<0.05).
CONCLUSIONS: The clinical implication of these findings as predictive factors for subsequent events such as malignant arrhythmias in patients taking 5-fluorouracil-based chemotherapy need longer follow-up and further detailed evaluations.
Institute of Oncology, University of Dokuz Eylul, Inciralti-Izmir, Turkey.