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Cancer Chemotherapy and Pharmacology
Published in: Cancer Chemotherapy and Pharmacology 5/2011

01-11-2011 | Short Communication

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

Authors: E. Giorgio, C. Caroti, F. Mattioli, V. Uliana, M. I. Parodi, Mauro D’Amico, C. Fucile, V. Marini, F. Forzano, G. Cassola, A. Martelli, F. Faravelli, E. Di Maria

Published in: Cancer Chemotherapy and Pharmacology | Issue 5/2011

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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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Metadata
Title
Severe fluoropyrimidine-related toxicity: clinical implications of DPYD analysis and UH2/U ratio evaluation
Authors
E. Giorgio
C. Caroti
F. Mattioli
V. Uliana
M. I. Parodi
Mauro D’Amico
C. Fucile
V. Marini
F. Forzano
G. Cassola
A. Martelli
F. Faravelli
E. Di Maria
Publication date
01-11-2011
Publisher
Springer-Verlag
Published in
Cancer Chemotherapy and Pharmacology / Issue 5/2011
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-011-1709-6

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