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Review
. 2021 Jul;28(7):2396-2402.
doi: 10.1111/ene.14857. Epub 2021 Apr 19.

Leukoencephalopathy with transient splenial lesions related to 5-fluorouracil or capecitabine

Valentine Perrain  1 , Kevin Bihan  2   3 , Flavie Bompaire  3   4 , Caroline Houillier  1 , Fanny Jomier  5 , Delphine Leclercq  6 , Sandrine Combret  7 , Julien Mahé  8 , Damien Ricard  3   4 , Giulia Berzero  1   9 , Dimitri Psimaras  1   3
Affiliations
Review

Leukoencephalopathy with transient splenial lesions related to 5-fluorouracil or capecitabine

Valentine Perrain et al. Eur J Neurol. 2021 Jul.

Abstract

Background: 5-Fluorouracil (5-FU) and its oral prodrug capecitabine have been rarely but consistently associated with acute central nervous system toxicity, including transient leukoencephalopathies involving the splenium of the corpus callosum.

Methods: We performed a retrospective search in the French Pharmacovigilance database (FPDB) (January 1985-July 2020) for adult patients affected by solid cancers who developed acute toxic leukoencephalopathies with splenial lesions following treatment with 5-FU or capecitabine. A comprehensive review of the literature helped to circumstantiate our findings.

Results: Our research in the FPDB identified six patients who, within 3 days from their first cycle of 5-FU or capecitabine, developed acute neurological symptoms, including gait ataxia (n = 4), dysarthria (n = 3), dysmetria (n = 2), headache (n = 2), and confusion (n = 2). Brain magnetic resonance imaging (MRI) showed T2/FLAIR (fluid-attenuated inversion recovery) hyperintensities in the corpus callosum, with diffusion restriction and no contrast enhancement, generally accompanied by additional alterations in the bilateral supratentorial white matter (n = 5). All patients discontinued the agent supposedly responsible for the toxicity and experienced full recovery after a median of 8.5 days from symptom onset. Control MRI showed a progressive normalization of acute MRI abnormalities. Literature review identified 26 cases with similar clinical and paraclinical characteristics. A single patient from the literature resumed 5-FU at a lower dose, with no recurrent toxicity.

Conclusions: 5-FU and capecitabine might be responsible for acute leukoencephalopathies with transient splenial lesions that are generally reversible upon drug discontinuation. Resuming the agent responsible for toxicity might be feasible in selected cases, after having excluded dihydropyrimidine dehydrogenase deficiency, if expected benefits outweigh the risks.

Keywords: 5-fluorouracil; capecitabine; corpus callosum; neurotoxicity; toxic leukoencephalopathy.

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References

REFERENCES

    1. Diasio RB, Harris BE. Clinical pharmacology of 5-fluorouracil. Clin Pharmacokinet. 1989;16(4):215-237.
    1. Femia G, Hardy TA, Spies JM, Horvath LG. Posterior reversible encephalopathy syndrome following chemotherapy with oxaliplatin and a fluoropyrimidine: a case report and literature review: PRES and chemotherapy. Asia Pac J Clin Oncol. 2012;8(2):115-122.
    1. Renouf D, Gill S. Capecitabine-induced cerebellar toxicity. Clin Colorectal Cancer. 2006;6(1):70-71.
    1. Couch LSB, Groteluschen DL, Stewart JA, Mulkerin DL. Capecitabine-related neurotoxicity presenting as trismus. Clin Colorectal Cancer. 2003;3(2):121-123.
    1. Xeloda product information [Internet]. [cited 2021 Feb 1]. Available from: https://www.ema.europa.eu/en/documents/product-information/xeloda-epar-p....

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