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

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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.

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Authors and Affiliations

  1. Hôpital d’Instruction des Armées Laveran, 13998, Marseille, France

    Pierre-Yves Cordier, André Nau, Manuela Oliver & Eric Peytel

  2. Laboratoire de Pharmacocinétique, CHU Timone, 13385, Marseille, France

    Joseph Ciccolini, Cédric Mercier & Bruno Lacarelle

Authors
  1. Pierre-Yves Cordier
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  2. André Nau
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  3. Joseph Ciccolini
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  4. Manuela Oliver
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  5. Cédric Mercier
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  6. Bruno Lacarelle
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  7. Eric Peytel
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Corresponding author

Correspondence to Pierre-Yves Cordier.

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Cordier, PY., Nau, A., Ciccolini, J. et al. 5-FU-induced neurotoxicity in cancer patients with profound DPD deficiency syndrome: a report of two cases. Cancer Chemother Pharmacol 68, 823–826 (2011). https://doi.org/10.1007/s00280-011-1666-0

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  • DOI: https://doi.org/10.1007/s00280-011-1666-0

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