Capturing Capecitabine Neurotoxicity: Delayed Clinical Manifestations of Capecitabine-Related Multifocal Leukoencephalopathy

Objective: NA Background: Capecitabine (Xeloda), a 5-Fluoruracil (5-FU) pro-drug, is a chemotherapy commonly used in the treatment of breast, colorectal and pancreatic cancers. A limited number of case reports exist describing multifocal leukoencephalopathy resulting from capecitabine toxicity. The clinical manifestations, which can range from nausea and vomiting to seizures and coma, are known to occur as early as 3–7 days following drug initiation or as late as 1–2 months later. Diagnosis is based on characteristic MRI findings of diffusion restriction along the white matter tracts. Discontinuation of capecitabine is known to lead to resolution of both clinical and radiologic findings within days to weeks. Design/Methods: NA Results: CASE: A 26-year-old woman with metastatic breast cancer was treated with capecitabine for 6 days. At day 3, she was experiencing nausea, vomiting, diarrhea, fever, and rash. By day 6, she also developed severe mucositis with dysphagia and odynophagia, requiring prompt hospitalization and eventual initiation of total parenteral nutrition. Her course was then complicated by febrile neutropenia, port-associated DVT and bacteremia, and massive hemorrhage from duodenal ulcers. By the sixth week of hospitalization, in spite of medical stabilization, she developed acute mental status changes with fluctuations in level of consciousness. MRI brain revealed diffusion restriction changes along the deep white matter tracts and splenium of the corpus callosum, consistent with the previously reported cases of both 5-FU and capecitabine-related neurotoxicity. CSF analysis showed normal cell count, glucose, and protein. Conclusions: The current literature describing capecitabine-related multifocal leukoencephalopathy suggests it occurs as an isolated neurologic syndrome, typically within days after treatment with capecitabine. In this case, manifestations of leukoencephalopathy were delayed until 7 weeks after last receiving capecitabine, and occurred in the setting of multiple other drug-related systemic toxicities. We suggest including an MRI brain in the evaluation of all capecitabine-treated patients who develop signs of an encephalopathy. Disclosure: Dr. Greenert has nothing to disclose. Dr. Katyal has nothing to disclose. Dr. Sung has nothing to disclose.