Fluorouracil induces myocardial ischemia with increases of plasma brain natriuretic peptide and lactic acid but without dysfunction of left ventricle

TY - JOUR

T1 - Fluorouracil induces myocardial ischemia with increases of plasma brain natriuretic peptide and lactic acid but without dysfunction of left ventricle

AU - Jensen, Søren Astrup

AU - Hasbak, Philip

AU - Mortensen, Jann

AU - Sørensen, Jens Benn

PY - 2010/12/20

Y1 - 2010/12/20

N2 - 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 NTproBNP 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.

AB - 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 NTproBNP 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.

U2 - 10.1200/jco.2009.27.3953

DO - 10.1200/jco.2009.27.3953

M3 - Journal article

SN - 0732-183X

VL - 28

SP - 5280

EP - 5286

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

IS - 36

ER -