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Severe fluoropyrimidine-related toxicity: clinical implications of DPYD analysis and UH2/U ratio evaluation

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Abstract

The fluoropyrimidines are commonly used in chemotherapeutic cancer medicine, but many patients still experience severe adverse side effects from these drugs. We observed a severe toxicity in a 50-year-old woman treated with capecitabine and docetaxel for a metastatic breast cancer. Since dihydropyrimidine dehydrogenase (DPD) is the main candidate for pharmacogenetic studies on 5-FU toxicity, the entire coding sequence and exon-flanking intronic regions of the DPYD gene were sequenced in the patient. None of the previously described deleterious variants were detected. Also, the haplotype-based analysis failed to reveal DPYD variations associated with 5-FU toxicity. We also evaluated the UH2/U ratio in plasma as an index of 5-FU pharmacokinetics. The UH2/U value did not demonstrate low DPD activity in the patient. We discuss the advantages and limitations of this approach, particularly concerning the clinical applications of 5-FU pharmacogenetics in the family setting.

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Acknowledgments

This work was partially granted by Italian Ministry of Education University and Research (PRIN 2007), Galliera Hospital and Fondazione Carige to EDM, Ministero della Salute to FF (Ricerca Finalizzata). VU is a PhD fellow at the University of L’Aquila, Italy. Biological samples were stored at the Galliera Genetic Bank—Telethon Genetic Biobank Network, supported by Italian Telethon onlus (project no. GTB07001A). The helpful contribution of Dr. AM Soldà and her team is gratefully acknowledged.

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Authors and Affiliations

  1. Laboratory of Genetics, Galliera Hospital, Genoa, Italy

    E. Giorgio & M. I. Parodi

  2. Division of Medical Oncology, Galliera Hospital, Genoa, Italy

    C. Caroti & Mauro D’Amico

  3. Department of Internal Medicine, Division of Clinical Pharmacology and Toxicology, University of Genova, Genoa, Italy

    F. Mattioli, C. Fucile, V. Marini & A. Martelli

  4. Department of Neuroscience, Ophthalmology and Genetics, University of Genova, Genoa, Italy

    E. Di Maria

  5. Division of Medical Genetics, Galliera Hospital, Via Volta, 6, 16128, Genoa, Italy

    V. Uliana, F. Forzano, F. Faravelli & E. Di Maria

  6. Division of Infectious Diseases, Galliera Hospital, Genoa, Italy

    G. Cassola

Authors
  1. E. Giorgio
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  2. C. Caroti
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  3. F. Mattioli
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  4. V. Uliana
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  5. M. I. Parodi
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  6. Mauro D’Amico
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  7. C. Fucile
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  8. V. Marini
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  9. F. Forzano
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  10. G. Cassola
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  11. A. Martelli
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  12. F. Faravelli
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  13. E. Di Maria
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Correspondence to E. Di Maria.

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Giorgio, E., Caroti, C., Mattioli, F. et al. Severe fluoropyrimidine-related toxicity: clinical implications of DPYD analysis and UH2/U ratio evaluation. Cancer Chemother Pharmacol 68, 1355–1361 (2011). https://doi.org/10.1007/s00280-011-1709-6

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  • DOI: https://doi.org/10.1007/s00280-011-1709-6

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