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Medline ® Abstracts for References 11,73

of 'Fluoropyrimidine-associated cardiotoxicity: Incidence, clinical manifestations, mechanisms, and management'

11
TI
Fluorouracil induces myocardial ischemia with increases of plasma brain natriuretic peptide and lactic acid but without dysfunction of left ventricle.
AU
Jensen SA, Hasbak P, Mortensen J, Sørensen JB
SO
J Clin Oncol. 2010;28(36):5280. Epub 2010 Nov 15.
 
PURPOSE: Fluorouracil (FU) is a cornerstone of colorectal cancer treatment; however, it has clinical and subclinical influence on the heart. This study aimed to clarify the pathophysiology, risk factors, and long-term effects of FU cardiotoxicity.
PATIENTS AND METHODS: The study prospectively accrued colorectal cancer patients (n=106) completely resected and adjuvantly treated with FU and oxaliplatin according to the FOLFOX4 regimen (infusional FU, folinic acid, and oxaliplatin). Serial measurements were made of systolic and diastolic features of the left ventricle by radionuclide ventriculography, plasma levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), lactic acid, and ECG before chemotherapy, immediately after a treatment infusion, and at follow-up 2 weeks after cessation of the intended 12 treatment courses and were further evaluated by multivariate regression analysis that included cardiovascular history and its risk factors.
RESULTS: In the entire cohort, NT-proBNP significantly increased from baseline 14.5±3.2 pmol/L (mean±standard error) to 28.3±5.3 pmol/L during FU therapy (P<.001). Nine patients (8.5%) with cardiotoxicity had significantly higher NT-proBNP of 55.3±40.8 pmol/L compared with 25.4±4.1 pmol/L in those without (P<.001). In multivariate analysis, the FU-induced rise of NT-proBNP was significantly higher in females (P<.001). Plasma lactic acid significantly increased from baseline (1.3±0.1 mmol/L to 1.8±0.1 mmol/L) during FU therapy (P<.001). Left ventricular ejection fraction at baseline of 0.66±0.01 remained unchanged at 0.65±0.01 during FU therapy and 0.66±0.01 at follow-up (P=.4).
CONCLUSION: FU therapy generally induces myocardial neuroendocrine changes with increasing plasma NT-proBNP and lactic acid but without long-term dysfunction of the left ventricle. The usability of NT-proBNP as a predictive marker for FU cardiotoxicity remains to be clarified.
AD
Rigshospitalet, Copenhagen University Hospital, and Department of Oncology 5073, University of Copenhagen, 9 Blegdamsvej, Copenhagen, DK-2100, Denmark. soren.a.jensen@mail.tele.dk
PMID
73
TI
5-Fluorouracil cardiotoxicity: left ventricular dysfunction and effect of coronary vasodilators.
AU
Patel B, Kloner RA, Ensley J, Al-Sarraf M, Kish J, Wynne J
SO
Am J Med Sci. 1987;294(4):238.
 
Seven patients developed clinical features simulating myocardial ischemia less than 72 hours after 12 of 13 separate intravenous 5-fluorouracil administrations; 9 episodes were associated with chest pain, 3 with hypotension, 3 with ventricular tachycardia and 1 with cardiogenic shock. Left ventricular dysfunction was demonstrated by echocardiography in 5 separate episodes, 2 with interval improvement upon repeat echocardiograms. Pretreatment with nitrates and/or calcium channel blockers failed to prevent recurrence of cardiotoxicity during 5 of 6 repeat 5-fluorouracil administrations. Therapy with 5-fluorouracil is associated with cardiotoxicity simulating myocardial ischemia with left ventricular dysfunction. Pretreatment with coronary vasodilators may not prevent this phenomenon.
AD
Department of Internal Medicine, Wayne State University School of Medicine, Detroit, Michigan.
PMID