Page 266 - Personalised medicine of fluoropyrimidines using DPYD pharmacogenetics Carin Lunenburg

Chapter 10
values in DPD phenotyping assays, but to analyse the results without categorizing patients. We discussed differences in DPD phenotyping assays, yet the endpoint toxicity can also influence the results. Variation in the outcome of severe toxicity might be caused by different types of treatment regimens between patients, which we did not correct for. As explained for DPD deficiency, analysing the data by categorizing patients also applies to the categorization of toxicity into severe (grade 3-5) and non-severe (grade 0-2) toxicity, where
grade 2 toxicity is a grey area in the assessment of toxicity.
Despite our unique data set, we were unable to show that any of the phenotyping assays
was associated with DPD deficiency or the onset of severe fluoropyrimidine-induced toxicity very well. The latter is possibly due to the fact that only ~30-50% of severe fluoropyrimidine- induced toxicity can initially be explained by DPD deficiency.33 Previously it was described that clinical validity and utility were not yet determined for all phenotyping assays,29 yet with this study we were unable to fully complement this lack of evidence.
Conclusion
We compared four DPD phenotyping assays (the endogenous dihydrouracil/uracil (DHU/U) ratio, endogenous uracil levels, the oral uracil loading dose, and the 2-13C-uracil breath test) in a first-time head-to-head comparison study. None of the phenotyping assays were associated with DPD deficiency or the onset of severe fluoropyrimidine-induced toxicity very well. In order to determine the clinical value of DPD phenotyping assays additional research is required.
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