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Upfront DPD Deficiency Detection to Secure 5-FU Administration: Part 2- Application to Head-and-Neck Cancer Patients

[ Vol. 4 , Issue. 2 ]

Author(s):

Manon Launay, Joseph Ciccolini*, Claire Fournel, Charlotte Dupuis, Nicolas Fakhry, Florence Duffaud, Sebastien Salas and Bruno Lacarelle   Pages 122 - 128 ( 7 )

Abstract:


Background: Upfront screening for dihydropyrimidine dehydrogenase (DPD) deficiency in patients scheduled for 5-FU should help to reduce the risk of toxicities by preventive adaptive dosing. Our group has developed a simple functional testing categorizing patients upon their DPD status, i.e. extensive metabolizer (EM) or poor metabolizer (PM) patients, using UH2/U ratio measurement in plasma as a surrogate for DPD activity. 5-FU dosing can be next tailored according to DPD deficiency status.

Objectives: We present here an observational study of this strategy implemented in routine clinical practice when treating head-and-neck cancer patients.

Results: A total of 218 evaluable adult patients were treated with a 5-FU-regimen, with DPD-based adaptive dosing. Among them, 20 (9%) were identified as PM and received subsequently a 20-50% reduced dosing of 5-FU as compared with EM patients (2102 ±254 mg VS. 2577 ±353mg, p<0.001 ttest). Gender (Female) was associated with higher risk for being PM (p=0.01, Pearson's Chi squared test). Overall, early severe toxicities were seen only in 5% of patients, all being EM with standard dosing. Similarly, overall severe toxicities were observed in 12.8% of patients only, both figures being markedly lower than usually reported with standard 5-FU. Despite the average -20% reduction in 5- FU dosing between PM and EM patients, clinical efficacy was not statistically different between the two groups (p = 0.2774, chi-square test).

Conclusion: This study shows that 5-FU-related toxicities can be greatly reduced in routine clinical practice by the upfront detection of DPD deficient patients with simple adaptive dosing strategy.

Keywords:

5-FluoroUracil, head and neck cancer, dihydropyrimidine dehydrogenase, adaptive dosing, DPD deficiency, efficacy, toxicity.

Affiliation:

Laboratoire de Pharmacocinetique Clinique, La Timone University Hospital of Marseille, APHM Marseille, Laboratoire de Pharmacocinetique Clinique, La Timone University Hospital of Marseille, APHM Marseille, Medical Oncology Unit, La Timone University Hospital of Marseille, APHM Marseille, Medical Oncology Unit, La Timone University Hospital of Marseille, APHM Marseille, Head-and-Neck Surgery Unit, La Conception University Hospital of Marseille, Marseille, Medical Oncology Unit, La Timone University Hospital of Marseille, APHM Marseille, Medical Oncology Unit, La Timone University Hospital of Marseille, APHM Marseille, Laboratoire de Pharmacocinetique Clinique, La Timone University Hospital of Marseille, APHM Marseille

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