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

Szczegóły
Abstrakt

Tytuł:: Leukoencephalopathy with transient splenial lesions related to 5-fluorouracil or capecitabine.
Autorzy:: Perrain V; AP-HP Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix, Service de Neurologie 2-Mazarin, Sorbonne Université, Inserm, CNRS, UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France.
Bihan K; Regional Pharmacovigilance Center, Department of Pharmacology, Pitié-Salpêtrière Hospital, Paris, France.; OncoNeuroTox Group, Center for Patients with Neurological Complications of Oncologic Treatments, Hôpitaux Universitaires Pitié-Salpêtrière-Charles Foix et Hôpital Percy, Paris, France.
Bompaire F; OncoNeuroTox Group, Center for Patients with Neurological Complications of Oncologic Treatments, Hôpitaux Universitaires Pitié-Salpêtrière-Charles Foix et Hôpital Percy, Paris, France.; Department of Neurology, Service de Santé des Armées, Hôpital d'Instruction des Armées Percy, Clamart, France.
Houillier C; AP-HP Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix, Service de Neurologie 2-Mazarin, Sorbonne Université, Inserm, CNRS, UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France.
Jomier F; Service de Neurologie, Hôpital Saint Joseph, Paris, France.
Leclercq D; Service de Neuroradiologie, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
Combret S; Department of Pharmacology, Regional Pharmacovigilance Center, Dijon, France.
Mahé J; Department of Pharmacology, Regional Pharmacovigilance Center, Nantes, France.
Ricard D; OncoNeuroTox Group, Center for Patients with Neurological Complications of Oncologic Treatments, Hôpitaux Universitaires Pitié-Salpêtrière-Charles Foix et Hôpital Percy, Paris, France.; Department of Neurology, Service de Santé des Armées, Hôpital d'Instruction des Armées Percy, Clamart, France.
Berzero G; AP-HP Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix, Service de Neurologie 2-Mazarin, Sorbonne Université, Inserm, CNRS, UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France.; Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Psimaras D; AP-HP Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix, Service de Neurologie 2-Mazarin, Sorbonne Université, Inserm, CNRS, UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France.; OncoNeuroTox Group, Center for Patients with Neurological Complications of Oncologic Treatments, Hôpitaux Universitaires Pitié-Salpêtrière-Charles Foix et Hôpital Percy, Paris, France.
Źródło:: European journal of neurology [Eur J Neurol] 2021 Jul; Vol. 28 (7), pp. 2396-2402. Date of Electronic Publication: 2021 Apr 19.
Typ publikacji:: Journal Article; Review
Język:: English
Imprint Name(s):: Publication: <2014- > : Oxford : Wiley
Original Publication: Oxford ; New York : Rapid Communications, [1994-
MeSH Terms:: Fluorouracil*/adverse effects
Leukoencephalopathies*/chemically induced
Leukoencephalopathies*/diagnostic imaging
Adult ; Antimetabolites, Antineoplastic/adverse effects ; Capecitabine/adverse effects ; Humans ; Retrospective Studies
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Contributed Indexing:: Keywords: 5-fluorouracil; capecitabine; corpus callosum; neurotoxicity; toxic leukoencephalopathy
Substance Nomenclature:: 0 (Antimetabolites, Antineoplastic)
6804DJ8Z9U (Capecitabine)
U3P01618RT (Fluorouracil)
Entry Date(s):: Date Created: 20210405 Date Completed: 20210812 Latest Revision: 20210812
Update Code:: 20240104
DOI:: 10.1111/ene.14857
PMID:: 33817933
: Czasopismo naukowe

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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.
(© 2021 European Academy of Neurology.)

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