5-fluorouracil-based therapy induces endovascular injury having potential significance to development of clinically overt cardiotoxicity.
Cancer Chemother Pharmacol
; 69(1): 57-64, 2012 Jan.
Article
em En
| MEDLINE
| ID: mdl-21603868
ABSTRACT
AIM:
This study aimed to elucidate the influence of 5-fluorouracil (5-FU)-based therapy on the vascular endothelium and its association with 5-FU-induced heart ischemia.METHODS:
The study prospectively accrued patients (n = 106) having completely resected colorectal cancer and receiving adjuvant treatment with 5-FU, folinic acid, and oxaliplatin. The levels of plasma von Willebrand factor (vWf), urine albumin-to-creatinine ratio (UACR), coagulation factor II + VII + X, and fibrin D-dimer were serially assessed before, during, and after chemotherapy.RESULTS:
The vWf level increased from median (range) 1.43 kU/l (0.48 to >3) to 2.64 kU/l (0.23 to >3) (P = 0.001), the UACR increased from 1.1 ± 0.2 mg/mmol (mean ± SE) to 2.1 ± 0.3 mg/mmol (P = 0.001), the coagulation factor II + VII + X activity decreased from 1.00 ± 0.02 to 0.94 ± 0.02 U/l (P = 0.001), and the fibrin D-dimer level increased from 1.1 ± 0.2 to 2.1 ± 0.3 kU/l (P = 0.001) at baseline and during chemotherapy, respectively. The changes in the levels of vWf (P = 0.3), UACR (P = 0.8), coagulation factor II + VII + X (P = 0.8), and fibrin D-dimer (P = 0.6) in nine (8.5%) patients having clinical signs of cardiotoxicity were not significantly different from that of the patients not having cardiotoxicity. The 5-FU-induced rise in plasma biomarkers was not significantly related to the cardiovascular morbidity or its risk factors (P = 0.9).CONCLUSIONS:
5-FU therapy induces global reversible endothelial injury leading to a procoagulant state. The ensuing endothelial dysfunction may be of significance to the pathogenesis of 5-FU-induced clinically overt cardiotoxicity. Cardiovascular disease is not significant for the vulnerability of the endothelium to 5-FU-based chemotherapy.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Tipo de estudo:
Etiology_studies
/
Observational_studies
Limite:
Adult
/
Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article