Capecitabine-induced multifocal leukoencephalopathy: A report of five cases

Videnović, Aleksandar; Semenov, I I; Chua-Adajar, R.; Baddi, Lisa; Blumenthal, Deborah T.; Beck, Anna; Simuni, Tatyana; Futterer, Stephen F.; Gradishar, William J.; Tellez, Claudia; Raizer, Jeffrey J.

doi:10.1212/01.wnl.0000187313.83515.7e

Cited by 77 publications

(46 citation statements)

References 8 publications

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“…After 5-FU is discontinued, most patients improve within a few days. 3 Lesions of 5-FU encephalopathy are most commonly seen in the deep white matter and corpus callosum. 2,3 This present case had clinical characteristics similar to those in previous reports.…”

Section: Case Reportmentioning

confidence: 99%

“…3 Lesions of 5-FU encephalopathy are most commonly seen in the deep white matter and corpus callosum. 2,3 This present case had clinical characteristics similar to those in previous reports. However, the MR imaging findings disclosed high signal intensities in unusual locations; diffusion-and T2-weightedimages showed involvement of the bilateral basal ganglia and thalami.…”

Section: Case Reportmentioning

confidence: 99%

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Atypical Diffusion-Restricted Lesion in 5-Fluorouracil Encephalopathy: Fig 1.

Lee

Kim

Son

et al. 2012

AJNR Am J Neuroradiol

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SUMMARY:Central nervous system toxicity of 5-FU could show various manifestations, such as decreased alertness, disorientation, and agitation. It is generally accepted that lesions of 5-FU encephalopathy are mainly in the deep cerebral white matter and corpus callosum on MR imaging. Here we describe a case of 5-FU encephalopathy in gastric cancer with an atypical reversible diffusion-restricted lesion on MR imaging, showing bilateral basal ganglia, thalami, and parasagittal frontal cortex involvement on diffusion and T2-weighted imaging.ABBREVIATIONS: BUN ϭ blood urea nitrogen; CRF ϭ chronic renal failure; DPD ϭ dihydropyrimidine dehydrogenase; 5-FU ϭ 5-fluorouracil; PT/INR ϭ prothrombin time/international normalized ratio 5-FU is a chemotherapeutic agent that is frequently used to treat breast, head and neck, colon, and stomach cancer. Among the neurotoxic effects of 5-FU, the cerebellar syndrome is the most frequent, whereas encephalopathy is uncommon and mostly reversible.1 Various symptoms of 5-FU encephalopathy include decreased alertness, disorientation, and agitation. It is generally accepted that 5-FU encephalopathy lesions seen on MR imaging are located mainly in deep white matter and the corpus callosum.2,3 Here, we describe a case of 5-FU encephalopathy with atypical diffusion-restricted lesions. Case ReportA 49-year-old man, who had undergone total gastrectomy for gastric cancer 3 months previously, was admitted for chemotherapy to the oncology division. He had a history of hypertension and CRF. He was taking ferrous sulfate, aspirin, furosemide, multivitamins, calcium carbonate, and erythropoietin. The patient had undergone hemodialysis 3 times weekly on a regular basis. He was not a heavy alcohol drinker, and there was no additional significant medical, social, or family history. On initial examination, the patient did not show any abnormal neurologic symptoms or signs. Routine laboratory data indicated anemia and CRF. BUN and creatinine levels fluctuated according to the hemodialysis schedule (36ϳ94 mg/dL and 4.7ϳ6.9 mg/dL, respectively).The patient was administered intravenous 5-FU (410 mg daily) and had no chemotherapy-related symptoms except nausea and vomiting. On the fourth day of the first cycle of 5-FU chemotherapy, he became semicomatose after a nap. He showed intermittent tremulous movement of all extremities and roving eye movements. All brain stem reflexes were intact. Brain MR imaging revealed diffusion restriction in the bilateral basal ganglia, thalami, and parasagittal frontal cortex. High-signal-intensity lesions were detected in the same locations on FLAIR imaging (Fig 1A). His serum ammonia level was high (265 g/dL; normal range, 0 -75 g/dL), and the PT/INR was prolonged to 1.85. His serum thiamine level was within normal limits (115.5 nmol/L), and BUN and creatinine levels were 50 mg/dL and 4.7 mg/dL, respectively. Other laboratory findings, including vitamin B1 and liver function, were unremarkable. An electroencephalogram showed continuous irregular mixed slowing without any e...

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Section: Case Reportmentioning

confidence: 99%

Section: Case Reportmentioning

confidence: 99%

Atypical Diffusion-Restricted Lesion in 5-Fluorouracil Encephalopathy: Fig 1.

Lee

Kim

Son

et al. 2012

AJNR Am J Neuroradiol

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“…As was seen in our patient, capecitabine-induced leukoencephalopathy is usually reversible after drug withdrawal, but sometimes, it may lead to life-threatening complications. 20) To the authors' knowledge, this is the first report of cardiomyopathy and cerebral leukoencephalopathy, both which are rare and life-threatening complications, being induced by capecitabine simultaneously. The association of dihydropyrimidine dehydrogenase (DPD) defi ciency with severe and generalized toxicity after administration of 5-FU has been reported.…”

Section: Discussionmentioning

confidence: 82%

“…Very few cases of capecitabine-induced cerebral leukoencephalopathy have been reported. 19,20) Leukoencephalopathy manifests as dizziness, memory defi cits, gait disturbances, confusion, and even coma. As was seen in our patient, capecitabine-induced leukoencephalopathy is usually reversible after drug withdrawal, but sometimes, it may lead to life-threatening complications.…”

Section: Discussionmentioning

confidence: 99%

Capecitabine Induces Both Cardiomyopathy and Multifocal Cerebral Leukoencephalopathy

et al. 2013

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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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“…Neurologic toxicity may manifest acutely as cerebellar syndrome as well as encephalopathy including cognitive impairment with somnolence, organic brain syndrome and dementia [1]. It may also manifest as a subacute multifocal leukoencephalopathy [2]. These symptoms are usually reversible on discontinuation of the drug.…”

Section: Discussionmentioning

confidence: 99%