the antimetabolite 5-fluorouracil ( fu ) is widely used in the treatment of solid tumors , including gastrointestinal , breast , head , and neck cancers .
cardiotoxicity , a rare adverse effect of 5-fu , has a reported incidence of 1.2% to 18% .
the patient presented with typical angina and electrocardiographic changes suggestive of an ischemic coronary event during the continuous infusion of 5-fu .
the ischemia recurred when the infusion was stopped , and was relieved by administration of nitroglycerin followed by a sublingual calcium channel blocker .
an 83-year - old man who had been diagnosed with stage iiic ( t4n2m0 ) adenocarcinoma of the ascending colon and who had undergone a right hemicolectomy was admitted to inje university seoul paik hospital to begin adjuvant chemotherapy , using the folfox4 regimen ( 400 mg / m 5-fu bolus infusion followed by the continuous infusion of 600 mg / m 5-fu for 22 hours on days 1 and 2 ; 200 mg / m leucovorin as a continuous infusion for 2 hours before 5-fu infusion on days 1 and 2 ; and infusion of 85 mg / m oxaliplatin on day 1 ) .
baseline echocardiography performed 1 month before admission showed normal left ventricular systolic function and no regional wall motion abnormality .
he was treated with 1,500 mg high - dose 5-fu ( 1,000 mg / m ) per day . on the morning of the 3rd day
, he developed a severe , substernal , crushing chest pain during the continuous intravenous infusion of 5-fu ( cumulative dose 1,679 mg / m ) , which was partially relieved by administering sublingual nitroglycerin .
the electrocardiogram ( ecg ) showed st segment elevation with a tall t wave in leads i , avl , and v4 - 6 , and reciprocal st segment depression in leads v1 - 2 ( fig .
the troponin - i and ck - mb levels were 0.010 ng / ml ( reference range ,  0.1 ) and 3.73 ng / ml ( reference range ,  4.94 ) , respectively .
severe hypokinesia of the lateral wall of the left ventricle was noted on a portable bedside echocardiogram .
the 5-fu infusion was stopped , and the chest pain and electrocardiographic changes resolved after intravenous infusion of nitroglycerin at 30 g / min .
emergency coronary angiography was then performed , which revealed significant stenosis in the proximal left circumf lex coronary artery ( lcx ) .
intracoronary nitroglycerin ( 200 g ) was injected to exclude coronary vasospasm , but no change occurred ( fig .
2 ) . intravenous ultrasound ( ivus ) showed severe luminal narrowing with a heavy concentric plaque in the proximal lcx .
percutaneous coronary intervention of the proximal lcx lesion was performed successfully with the implantation of a drug - eluting stent ( 3.5  16 mm ; taxus , national medical center , seoul , korea ) ( fig .
the patient was transferred to the coronary - care unit , where 8 hours later , he reported a recurrence of the anterior chest pain .
the ecg also showed st segment elevation and reciprocal st changes similar to those seen in the previous ischemic events ( fig .
the chest pain and ecg changes persisted despite a 100 g / min nitroglycerin infusion . to rule out acute stent thrombosis ,
the chest pain and ecg changes were relieved after sublingual administration of 10 mg nifedipine . repeated coronary angiography showed a widely patent stent ( fig .
4 ) . the postprocedural troponin - i and ck - mb levels were 0.010 and 4.62 ng / ml , respectively .
echocardiography performed the next day also showed the absence of the regional wall motion abnormality and normal left ventricular systolic function .
we present here a case of severe cardiotoxicity mimicking acute anterolateral myocardial infarction occurring in a patient receiving 5-fu chemotherapy for adenocarcinoma of the colon .
the cessation of 5-fu administration and the subsequent initiation of treatment with a sublingual calcium channel blocker and nitrate resulted in a successful outcome .
although the mechanism by which 5-fu exerts its cardiotoxic effects is unknown , the resolution of the patient 's chest pain and the normalization of his ecg changes with a vasodilator strongly support the vasospastic hypothesis of 5-fu cardiotoxicity .
one study postulated that 5-fu - associated cardiotoxicity is due to the uncoupling of the electromechanical mechanisms that underlie normal myocardial function , which might be mediated at the level of the cell membrane .
recently , kuzel et al .   suggested that 5-fu promotes a hypercoagulable state ( e.g. , coronary artery thrombosis ) and observed a significant increase in fibrinopeptide a and a decrease in protein c activity during 5-fu administration . the incidence of clinically apparent 5-fu cardiotoxicity is less than 10% in patients receiving the drug .
patients with a history of coronary artery disease ( cad ) have a significantly increased risk of 5-fu - induced cardiotoxicity .
although our patient did not have a history of cad , a large atheromatous plaque was found on coronary angiography and ivus .
therefore , during 5-fu infusion , close , careful monitoring of patients , especially those with pre - existing cad or cad risk factors , is mandatory .
prophylactic calcium channel blockers or nitrates should be administered to patients with cad during 5-fu administration , to prevent vasospasm .
one study proposed that impaired renal function is also a risk factor for 5-fu cardiotoxicity .
although it is not clear whether the cardiotoxic metabolites undergo renal excretion , the pathophysiological effect of 5-fu on the myocardium is likely to increase with decreased renal function .
thus it is necessary to clarify which patients may benefit from optimum anti - angina prophylaxis and careful , close monitoring .
the incidence of 5-fu - related cardiotoxicity appears to be dependent on the dosage and delivery system .
infusion of 5-fu , which is now being used more frequently and at higher doses instead of bolus therapy , may be a significant factor in the development of 5-fu cardiotoxicity . in one study ,
nine patients treated with a higher - dose ( > 800 mg / m ) continuous infusion of 5-fu died suddenly . interestingly , despite stopping the 5-fu , the chest pain and ecg changes recurred in our case .
one series reported that 19% of the patients developed reversible angina pectoris during treatment , which lasted for up to 12 hours after cessation of the infusion .
the possible mechanisms of delayed angina are the late release of potent vasoactive 5-fu metabolites , which accumulate over time due to degradation of 5-fu .
therefore , a calcium channel blocker or nitrates should be administered after stopping the 5-fu when 5-fu - induced cardiotoxicity occurs .
the long - term outcome of patients with 5-fu - related cardiotoxicity has not been investigated extensively . as with our case ,
patel et al .   recently reported interval improvements in the left ventricular wall motion abnormalities in echocardiography performed 8 to 15 days following the initial study .
when cardiotoxicity occurs , 5-fu treatment is usually discontinued due to its very high recurrence rate ( 90% )
. the re - administration of 5-fu is not recommended , and a different chemotherapy regimen should be considered .
interestingly , meydan et al .   continued 5-fu chemotherapy in one group who experienced 5-fu cardiotoxicity due to the absence of an alternative drug and found that subsequent serious , hemodynamic consequences were easily controlled with nitrate treatment . for the remaining patients ,
either 5-fu was removed from the combination regimen or an alternative drug was started and no cardiotoxicity developed subsequently . in summary , although 5-fu - associated cardiac toxicity is rare , it may cause angina , myocardial infarction , and even sudden death .
physicians should be aware of this potentially lethal side effect and should start the proper treatment when 5-fu cardiotoxicity develops .
this case supports the vasospastic hypothesis of 5-fu cardiac toxicity , indicating that a calcium channel blocker may be effective for prevention or treatment of 5-fu cardiotoxicity .
 cardiotoxicity associated with 5-fluorouracil ( fu ) is an uncommon , but potentially lethal , condition . 
 the case of an 83-year - old man with colon cancer who developed chest pain during 5-fu infusion is presented . 
 the electrocardiogram ( ecg ) showed pronounced st elevation in the lateral leads , and the chest pain was resolved after infusion of nitroglycerin . a coronary angiogram ( cag ) revealed that the patient had significant atherosclerosis in the proximal left circumflex artery . 
 coronary artery spasm with fixed stenosis was considered , and a drug - eluting stent was implanted . 
 after 8 hours , the patient complained of recurring chest pain , paralleled by st elevation on the ecg . 
 the chest pain subsided after administration of intravenous nitroglycerin followed by sublingual nifedipine . 
 repeated cag showed patency of the previous stent . 
 this case supports the vasospastic hypothesis of 5-fu cardiac toxicity , indicating that a calcium channel blocker may be effective in the prevention or treatment of 5-fu cardiotoxicity . 