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Journal of Clinical Oncology, Vol 24, No 18 (June 20), 2006: pp. 2959-2960 © 2006 American Society of Clinical Oncology. DOI: 10.1200/JCO.2005.04.0766
Acute Coronary Syndrome Secondary to Fluorouracil InfusionState University of New York Upstate Medical University, Syracuse, NY The patient, a 41-year-old man, presented with a neck mass on his right side, and was diagnosed with stage IV (T3N3M0) squamous cell carcinoma of the right tonsillar fossa. The patient underwent radical neck dissection, as well as radiation therapy for his squamous cell carcinoma, and did well for 1.5 years. Subsequently, the patient was found to have recurrence when a lung mass as well as a bony metastasis was found in his left shoulder. The patient was entered onto a clinical trial and was randomly assigned to the standard treatment arm with cisplatin and infusional fluorouracil (FU). The patient was admitted to begin his chemotherapy and was given cisplatin as well as a 5-day continuous infusion of FU. The patient was treated with 1,000 mg/m2 per day, which was calculated to be 2,210 mg in 500 mL normal saline. He developed severe substernal chest pain on the morning of the third day, which was partially relieved by nitroglycerin. The patient had mild ST elevation in leads II, III, AVF, and V4-V6 (Fig 1).
He also had an elevated troponin, with a peak of 18.6. A diagnosis of acute ST elevation myocardial infarction was made. The patient's echocardiogram at that time showed that there was global hypokinesis with an ejection fraction of 25%. He was taken emergently for cardiac catherization, which revealed that he had normal coronaries without any evidence of plaque, stenosis, or vasospasm (Figs 2 and 3). The patient transiently required pressor support with dobutamine, but was able to be sent home safely. Repeat echocardiogram performed 3 weeks after the myocardial infarction showed that his ejection fraction had improved to 50% with only mild global hypokinesis. Finally, another repeat echocardiogram performed 2 months after the myocardial infarction showed that his ejection fraction had recovered to 65% and that the global hypokinesis had entirely resolved.
There have been case reports in the literature documenting the incidence of cardiotoxicity due to fluorouracil infusions. In one prospective study of 367 patients, de Forni et al1 found that the incidence of high-dose FU continuous infusion related cardiotoxicity was 7.6%. There were ECG changes in 65% of patients with cardiac events. However, only two of their 28 patients with cardiac events had elevated cardiac enzymes, and nine of 16 patients who were examined were noted to have partial or global hypokinesia. However, in a large retrospective study of 1,083 patients, the incidence of FU cardiotoxicity was reported to be 1.6% with bolus dosing.2 Meydan and Kundak3 found that the incidence of cardiac events was 3.9% in a population of 231 patients receiving de Gramont's regimen (2 days infusional FU). Oztop and Gencer4 found significant prolongations of QT interval in 22 patients without overt cardiac disease. These patients were also found to have no echocardiographic nor cardiac enzyme changes with the bolus plus infusional FU. Sudhoff and Enderle5 found that FU infusion can actually induce arterial vasocontractions. They used high-resolution ultrasound to evaluate the diameter of the brachial artery in patients receiving infusional FU. Fifty percent of the 30 patients receiving FU showed brachial artery constriction, whereas none of the patients receiving non-FU chemotherapy showed constriction. Vessel tone returned to normal within 30 minutes after stopping FU. Vessel contractions reoccurred in 86% of these patients. In additional, patients that were pretreated with glyceroltrinitrate showed no contraction of the brachial artery. The young age, dramatic presentation, and documented absence of pre-existing coronary artery disease on coronary angiography in our patient make the case relatively unique. Many of the currently used chemotherapy regimens for gastrointestinal malignancies integrate the use of newer agents, like irinotecan, oxaliplatin, and bevacizumab, with fluorouracil infusions (eg, oxaliplatin plus FU/leucovorin [FOLFOX] and folinic acid plus FU and irinotecan [FOLFIRI] regimens). With the demonstrated efficacy of these new chemotherapy regimens, more patients will be receiving these agents in the future. Often in the United States, infusional FU is administered at home via an infusional pump. Therefore, it is important for clinicians need to be aware of this rare but potentially serious adverse effect of infusional fluorouracil and to counsel patients, family, and nursing staff, accordingly. Factors predisposing to acute cardiac toxicity of infusional FU should be investigated. Authors' Disclosures of Potential Conflicts of Interest The authors indicated no potential conflicts of interest.
REFERENCES
1. de Forni M, Malet-Martino MC, Jaillais P, et al: Cardiotoxicity of high dose continuous infusion fluorouracil: A prospective clinical study. J Clin Oncol 10:1795-1801, 1992 2. Labianca R, Berreta G, Clerici M, et al: Cardiac toxicity of 5FU: A study of 1,083 patients. Tumori 68:505-510, 1981 3. Meydan N, Kundak I, Yavuzsen T, et al: Cardiotoxicity of de Gramont's Regimen: Incidence, clinical characteristics and long-term follow-up. Japanese J Clin Oncol 35:265-270, 2005 4. Oztop I, Gencer M, Okan T, et al: Evaluation of cardiotoxicity of combined bolus and infusional fluorouracil/folinic acid treatment by echocardiography, plasma troponin I level, QT interval and dispersion in patients with gastrointestinal system cancers. Japanese J Clin Oncol 34:262-268, 2004 5. Sudhoff T, Enderle MD, Pahlke M, et al: 5-Fluorouracil induces arterial vasocontractions. Ann Oncol 15:661-664, 2004
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Copyright © 2006 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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