Capecitabine Induces Both Cardiomyopathy and Multifocal Cerebral Leukoencephalopathy

Abstract

SummaryChemotherapy for malignant tumors has diversifi ed, and recognizing its side effects has become more important than ever. Both cardiotoxicity and neurotoxicity are rare, but they are among the most serious side effects caused by 5-fl uorouracil (5-FU). Capecitabine is an orally administered prodrug that converts preferentially to 5-FU within tumors, resulting in enhanced concentrations of 5-FU in tumor tissue. Given that it targets tumor tissue, capecitabine was expected to reduce the risk of side effects associated with fl uoropyrimidine. Here, we present the case of a 62-year-old man with colorectal adenocarcinoma who simultaneously experienced cardiomyopathy with cardiogenic shock and cerebral leukoencephalopathy during treatment with capecitabine. During emergency coronary angiography, ST-segment elevation and severely reduced left ventricular wall motion were observed; however, no severe coronary stenosis or spasm was revealed. Furthermore, we present a review of the literature on capecitabine-induced cardiotoxicity. As of April 2013, 39 case reports on capecitabine-induced cardiotoxicity have been published; however, cardiomyopathy was very rare, with only 3 cases reported. It is important for physicians to be aware of the various rare, but potentially serious, adverse effects associated with capecitabine chemotherapy and to inform patients about the possibility of these side effects, including cardiotoxicity and neurotoxicity. (Int Heart J 2013; 54: 417-420) Key words: Chemotherapy, Cardiotoxicity, Neurotoxicity R ecently, chemotherapy for malignant tumors has diversifi ed, and recognizing the side effects of chemotherapy as well as its curative effects has become more important than ever. Many anticancer drugs are cardiotoxic, and it is well known that both anthracycline antibiotics and trastuzumab cause congestive heart failure.1) Five-fluorouracil (5-FU) is one of the most important chemotherapeutic agents used to treat many solid tumors, including colorectal cancer; however, it has several adverse effects.2) Cardiotoxicity 3) and cerebral leukoencephalopathy 4) are rare side effects of 5-FU therapy, but are among the more serious side effects associated with this therapy. Capecitabine, an orally administered fl uoropyrimidine carbamate, is a 5-FU prodrug that was developed to lessen the side effects associated with 5-FU therapy.5) Oral 5-FU often causes intestinal tract toxicity, and oral administration of high-dose 5-FU raises the concentration of the drug in the intestinal tract; therefore, intestinal tract toxicity is often the dose-limiting factor. Capecitabine itself is not cytotoxic, but it becomes effective after it has been converted to 5-FU in tumor cells. 5,6) It is widely used because it can be orally administered and is associated with fewer side effects.2) However, as the use of capecitabine becomes more widespread, its side effects, including cardiotoxicity, appear to be similar to those of 5-FU.3,7) We report a case of cardiomyopathy mimicking acute coronary syndrome that coin...

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“…55, 56 However, adverse effects by the inherent toxicity of the drugs are inevitable. 57–60 Targeting oncogenic protein kinase signaling pathways has reduced the off-targeting effect and non-specific toxicity. 61, 62 In spite of the benefits, the complicated therapeutic mechanism 63, 64 and the new adverse effects 65, 66 of targeted agents limit the clinical outcomes for cancer patients.…”

Takotsubo cardiomyopathy in cancer patients

“…These cases occurred in patients between 47 and 81 years of age with a similar incidence between the two genders. These patients did not have a past history of CAD and were undergoing treatment of either colorectal cancer (3 cases) [20,28,29] or metastatic breast cancer (2 cases) [27,30]. All of the TCM cases occurred during the first cycle of capecitabine treatment with the exception of one case that had received 5 prior cycles of 5-FU before being switched to capecitabine.…”

Permanent lesion to the corticospinal tract after therapy with capecitabine

“…Toxic leukoencephalopathy and lesion to the corticospinal tract is a severe side effect of chemotherapy with fluoropyrimidine capecitabine, which is used to treat colorectal and breast cancer 1–8…”

“…Capecitabine is a prodrug of 5-fluorouracil (5-FU) used to treat colorectal and breast cancer. Toxic encephalopathy induced by capecitabine is a rare but severe side effect that has consistently been reported over the last 15 years 1–7. Involvement of the bilateral corticospinal tract in capecitabine-induced leukoencephalopathy has also been described 8.…”