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Clinical Fellow in Medical Oncology Department of Medical Oncology Hacettepe University Institute of Oncology 06100, Sihhiye Ankara, Turkey fax 90-3123242009 saksoy07{at}yahoo.com
Assistant Doctor Department of Internal Medicine Hacettepe University Faculty of Medicine
Clinical Fellow Department of Medical Oncology Hacettepe University Institute of Oncology
uayib Yalçin, MD
Professor of Medical Oncology Department of Medical Oncology Hacettepe University Institute of Oncology
Published Online, February 8, 2005. www.theannals.com, DOI 10.1345/aph.1E252
We report a patient who had angina pectoris due to coronary spasm during continuous infusion of fluorouracil and oral capecitabine administration at separate times.
Case Report. A 57-year-old 89-kg male patient was diagnosed with a moderately differentiated adenocarcinoma of the colon with multiple unresectable liver metastases. Following left hemicolectomy, chemotherapy for the liver metastases was initiated, consisting of intravenous irinotecan 180 mg/m2 on day 1 with a fluorouracil 400-mg/m2 bolus and 600-mg/m2 intravenous infusion given over 22 hours, plus intravenous folinic acid 200 mg/m2 on days 1 and 2, administered every 2 weeks. During the first day of infusion at the 18th hour, the patient developed angina pectoris. An electrocardiogram (ECG) showed a 0.5-1-mm ST elevation in leads V1-V3. Troponin T levels were also found to be elevated. Infusion of fluorouracil was stopped, and therapy with intravenous nitrates and low-molecular-weight heparin was started. Coronary angiography was performed 24 hours later, and no lesion was found in the coronary arteries. Diagnosis of coronary vasospasm was established, and the antianginals calcium-channel blockers, nitrates, and aspirin were prescribed.
The patient was overweight, but serum cholesterol levels were normal. He was an ex-smoker (quit 10 y ago). Due to the fluorouracil-induced coronary spasm, chemotherapy was switched to a combination of capecitabine 1000 mg/m2/day orally twice daily on days 1-14, plus intravenous irinotecan 250 mg/m2 on day 1, once every 3 weeks. During the second day of treatment after the third dose of capecitabine, the patient again experienced typical angina pectoris symptoms that lasted for 20 minutes and responded to oral nitrates. ECG revealed no changes, and cardiac enzyme levels were normal.
After this second attack, chemotherapy was changed again, and the patient began irinotecan as a single agent. During the infusion of irinotecan, the patient did not experience angina pectoris. Since the cardiotoxicity of capecitabine was not as well recognized as with fluorouracil and because there were no ECG and cardiac enzyme changes, a rechallenge with irinotecan/capecitabine combination therapy was performed. On the second day of treatment, the patient again experienced angina pectoris at rest that lasted for 15-20 minutes and was relieved with oral nitrates. The diagnosis of angina pectoris due to capecitabine was established, and therapy was discontinued. The patient has since then been treated with irinotecan monotherapy, 350 mg/m2 intravenously once every 3 weeks, and has not experienced angina pectoris.
Discussion. Although coronary artery vasospasm, direct toxicity to the myocardium, thrombogenic effects, and autoimmune phenomena have been proposed as etiologies of fluorouracil cardiotoxicity, the exact mechanism of the adverse cardiac effects of this drug or its metabolites has not been elucidated.4,5 Use of the Naranjo probability scale indicated a probable relationship between cardiotoxicity and capecitabine in this patient.6 This case demonstrates that capecitabine can induce severe chest pain similar to that experienced with fluorouracil and that a positive history of fluorouracil cardiotoxicity may be a risk factor for capecitabine cardiotoxicity.
References
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