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Cancer Chemother Pharmacol. 2011 Sep;68(3):823-6. doi: 10.1007/s00280-011-1666-0. Epub 2011 May 8.

5-FU-induced neurotoxicity in cancer patients with profound DPD deficiency syndrome: a report of two cases.

Author information

1
Hôpital d'Instruction des Armées Laveran, Marseille, France. pierre-yves.cordier@laposte.net

Abstract

PURPOSE:

5-Fluorouracil (5-FU) is a mainstay for treating various solid tumours in adults, including digestive and head and neck cancers. 5-FU-related toxicities usually include haematological, digestive and cutaneous features. Additionally, 5-FU has been described as being potentially neurotoxic in patients, but these side effects are quite rare in clinical practice. Here, we report two cases of sudden and unpredictable drug-induced neurotoxicities that occurred in patients undergoing their first course of 5-FU-based chemotherapy.

PATIENTS AND METHODS:

None of these patients had any previous neurological disorder history, and both were treated following standard regimen (LV-5-FU2 and TPF for patient 1 and 2, respectively). Neurotoxicity included drowsiness, acute confusion plus dysarthria for the first patient and seizure, confusion and signs of metabolic encephalopathy for the second one. In addition, typical 5-FU-related severe toxicities (e.g. neutropenia and mucosities) were observed. Both patients slowly recovered from these neurological toxicities under supportive treatment. It was assumed that overexposure to 5-FU could explain the severe toxicities encountered. To test this hypothesis, we retrospectively evaluated the dihydropyrimidine dehydrogenase (DPD) activity of these patients on a phenotypic basis.

RESULTS:

Evaluation of the uracil-to-di-hydrouracil (U/UH2) ratio in plasma revealed a profound DPD deficiency syndrome in both patients.

CONCLUSION:

These cases suggest that 5-FU standard dosage administration may lead to strong overexposure, responsible for the severe toxicities observed, including the neurological features. It implies that DPD deficiency can cause neurotoxicity in 5-FU-treated patients and advocates for the prospective screening of DPD deficiency before starting any 5-FU-containing chemotherapy so as to prevent such side effects in the future.

PMID:
21553285
DOI:
10.1007/s00280-011-1666-0
[Indexed for MEDLINE]

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