Medline ® Abstracts for References 63,66-68
of 'Fluoropyrimidine-associated cardiotoxicity: Incidence, clinical manifestations, mechanisms, and management'
5-Fluorouracil induces arterial vasocontractions.
Südhoff T, Enderle MD, Pahlke M, Petz C, Teschendorf C, Graeven U, Schmiegel W
Ann Oncol. 2004;15(4):661.
BACKGROUND: From 2% to 10% of cancer patients treated with 5-fluorouracil (5-FU) will develop symptomatic cardiotoxicity. Nevertheless, the underlying pathophysiology is mostly unknown.
PATIENTS AND METHODS: We investigated the influence of intravenous chemotherapy (CTX) on the diameter of the brachial artery using high resolution ultrasound in patients with malignant tumors, mostly gastrointestinal cancer. Cytostatic drugs included 30 cases with 5-FU and 30 cases with non-5-FU CTX (cis/carboplatin, anthracycline and cyclophosphamide). In addition, plasma levels of big endothelin were assessed prior to and after CTX.
RESULTS: Fifteen of 30 patients (50%) showed a contraction of the brachial artery after the end of 5-FU application (median 11%, range 4.3-18.5), whereas no single contraction was noticed in 30 patients following non-5-FU-based CTX. Vessel tonus generally normalized within 30 min after stopping 5-FU. Five patients positive for 5-FU associated vessel contraction were repeatedly exposed to 5-FU. Vessel contractions reoccurred in 86% (18/21) of these administrations. When patients with 5-FU bolus application were pre-treated with glyceroltrinitrate no contraction of the brachial artery was detected in five out of five occasions. There was a trend towards increased big endothelin plasma levels after 5-FU application (median 1.52 versus 1.99 fmol/ml; P = 0.07), whereas big endothelin levels remained unchanged after non-5-FU CTX (1.83 versus 1.83 fmol/ml; P = 0.99).
CONCLUSIONS: Application of 5-FU is commonly accompanied by arterial vessel contractions, which is likely to represent the first step in 5-FU-induced cardiotoxicity. 5-FU-associated vessel contractions were highly reproducible on re-exposure and were in the case of bolus application completely preventable by glyceroltrinitrate.
Department of Internal Medicine, Ruhr-University Bochum, Knappschaftskrankenhaus, Bochum, Germany. firstname.lastname@example.org
Prinzmetal's angina during 5-fluorouracil chemotherapy.
Kleiman NS, Lehane DE, Geyer CE Jr, Pratt CM, Young JB
Am J Med. 1987;82(3):566.
Variant angina developed during intravenous 5-fluorouracil therapy in a patient without prior history of angina pectoris. Ambulatory electrocardiography demonstrated S-T segment elevation and ventricular ectopy during pain, whereas no symptoms or S-T segment changes occurred during placebo therapy. Prophylaxis with both nifedipine and diltiazem was successful in preventing recurrence. It is believed that 5-fluorouracil induced coronary vasospasm and that this was prevented by prophylactic calcium antagonist therapy. Drug-induced coronary artery spasm may be the cause of 5-fluorouracil-associated chest pain.
Coronary artery spasm induced by 5-fluorouracil.
Luwaert RJ, Descamps O, Majois F, Chaudron JM, Beauduin M
Eur Heart J. 1991 Mar;12(3):468-70.
We report a case of coronary artery spasm induced by 5-fluorouracil. The symptoms occurred during continuous intravenous infusion of the drug, and a coronary spasm was visualized at angiography.
Division of Cardiology, Hôpital de Jolimont, Haine-Saint-Paul, Belgium.
5-fluorouracil-induced coronary vasospasm.
Shoemaker LK, Arora U, Rocha Lima CM
Cancer Control. 2004 Jan-Feb;11(1):46-9.
BACKGROUND: Cardiotoxicity is a rare but well-documented adverse effect of 5-fluorouracil (5-FU). The underlying cause of this side effect of 5-FU is uncertain.
METHODS: We present a case report of a 63-year-old man treated for metastatic colon cancer who experienced chest pain while being treated with the FOLFIRI regimen. This case report documents coronary artery spasm on catheterization observed with the continuous infusion of 5-FU.
RESULTS: Cardiac catheterization obtained within 36 hours of the onset of chest pain revealed marked coronary vasospasm in the obtuse marginal coronary artery and a right coronary artery with a critical obstructive atherosclerotic plaque. Electrocardiogram revealed the myocardium area associated with the event was diffuse rather than localized to the right coronary artery.
CONCLUSIONS: This observation supports the vasospastic hypothesis for 5-FU-induced angina. Although rare, this type of cardiotoxicity with 5-FU is a potentially lethal side effect. Therapy with 5-FU should be discontinued and patients should be promptly treated.
Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, OH 44195, USA. email@example.com