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Medline ® Abstracts for References 74-77

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

74
TI
Severe cardiotoxicity during 5-fluorouracil chemotherapy: a case and literature report.
AU
Kuropkat C, Griem K, Clark J, Rodriguez ER, Hutchinson J, Taylor SG 4th
SO
Am J Clin Oncol. 1999;22(5):466.
 
The chemotherapeutic agent 5-fluorouracil (5-FU) is a widely accepted part of many cancer treatment protocols. Its cardiotoxic potential is known, but considered uncommon and usually not life threatening, although some cases of severe cardiotoxicity related to 5-FU have been reported. The pathogenesis of cardiotoxicity caused by 5-FU is not clear. We report a case of sudden onset of severe cardiac failure, without ischemic symptoms or signs, during 5-FU treatment with serious consequences, in a previously healthy 23-year-old patient with squamous cell carcinoma of the tongue. Endomyocardial biopsy showed proliferation of the sarcoplasmic reticulum with marked vacuolization, similar to that found with doxorubicin cardiotoxicity. Because 5-FU cardiotoxicity is unpredictable and can have potentially fatal consequences, it requires, in our opinion, further clarification. With this well-documented case, including an endomyocardial biopsy, we hope to encourage additional efforts to investigate the pathophysiologic mechanisms of 5-FU cardiotoxicity.
AD
Rush Cancer Institute, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois, USA.
PMID
75
TI
The appearance of endothelium in small arteries after treatment with 5-fluorouracil. An electron microscopic study of late effects in rabbits.
AU
Cwikiel M, Eskilsson J, Wieslander JB, Stjernquist U, Albertsson M
SO
Scanning Microsc. 1996;10(3):805.
 
Cardiotoxicity is an unexplained toxic manifestation of 5-fluorouracil (5-FU). Its possible mechanism could be a direct cytotoxic effect on the vascular endothelium. We have tested this hypothesis in an experimental study in rabbits, using scanning and transmission electron microscopic evaluation of endothelium in small arteries (the central artery of the ear). The perfusion fixation method at physiological pressure and temperature was used. Both local and systemic effects of 5-FU on endothelium were studied 1, 3, 7, 14 and 30 days after in vivo treatment with 5-FU. Fifteen rabbits were used and five additional animals served as controls. The following parameters were evaluated: vessel wall and endothelial cell contraction, cell oedema, cytolysis, occurrence of denuded areas, platelet adhesion/aggregation and fibrin formation. For the description of each parameter, a scale of negative points (0.0-3.0) was used. We found severe cell damage with accompanying thrombus formation. The findings support the hypothesis that the thrombogenic effect of 5-FU, secondary to its direct cytotoxic effect on endothelium, is the pathophysiological mechanism behind 5-FU cardiotoxicity.
AD
Department of Oncology, University Hospital, Lund, Sweden. wojciech.cwikiel@mailbox.swipnet
PMID
76
TI
5-Fluorouracil related toxic myocarditis: case reports and pathological confirmation.
AU
Sasson Z, Morgan CD, Wang B, Thomas G, MacKenzie B, Platts ME
SO
Can J Cardiol. 1994;10(8):861.
 
This report describes two cases of cardiotoxicity associated with the use of 5-fluorouracil (5-FU) in the treatment of neoplastic disease, and reviews the literature to date. The manifestations of cardiac toxicity were significant ventricular dysfunction during continuous infusion of 5-FU, accompanied by symptoms resembling cardiac ischemia in one case and irreversible cardiogenic shock in another. Detailed cardiac investigations and pathological findings provide convincing evidence that the development of acute myocarditis is the likely mechanism of 5-FU cardiotoxicity, rather than coronary insufficiency as has commonly been postulated. Although cardiotoxicity as a complication of 5-FU therapy remains rare, recognition of this entity is important as it may lead to serious hemodynamic compromise and may recur with drug rechallenge.
AD
Department of Medicine, The Wellesley Hospital, Toronto, Ontario.
PMID
77
TI
5-fluorouracil-based therapy induces endovascular injury having potential significance to development of clinically overt cardiotoxicity.
AU
Jensen SA, Sørensen JB
SO
Cancer Chemother Pharmacol. 2012;69(1):57. Epub 2011 May 21.
 
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.
AD
Department of Oncology 5073, Rigshospitalet, Copenhagen University Hospital, 9 Blegdamsvej, 2100 Copenhagen, Denmark. soren.a.jensen@mail.tele.dk
PMID