Page 199 - Personalised medicine of fluoropyrimidines using DPYD pharmacogenetics Carin Lunenburg

Fluoropyrimidine dosages in chemoradiation therapy
and 9.1 and 9.1% for DPYD variant allele carriers who received a reduced dose, respectively (Figure 1, Table 3). DPYD variant allele carriers treated with a standard dose had a significantly increased risk to develop severe gastrointestinal toxicity (adjusted OR: 2.58, 95% confidence interval [95%CI]: 1.023─6.534, p=0.045) and severe haematological toxicity (adjusted OR:4.19, 95%CI: 1.323─13.253, p=0.015) compared with DPYD wild-type patients treated with standard dose. No statistical significant difference was found for the risk of developing severe gastrointestinal toxicity (adjusted OR: 1.10, 95%CI: 0.250─4.804, p=0.904) or severe haematological toxicity (adjusted OR: 3.88, 95%CI: 0.837─18.016, p=0.083) in DPYD variant allele carriers who received an initially reduced dose compared with wild-types. Grouped diagnosis was not significantly associated with the development of severe gastrointestinal toxicity (adjusted OR: 0.26, 95%CI: 0.061─1.069), while it was for severe haematological toxicity (adjusted OR: 4.21, 95%CI: 1.760─10.053, p=0.001), with more toxicity in pelvic malignancies.
7
OR: 2.58
p=0.045
5 0
W ild-type + standard dose DPYD + standard dose DPYD + reduced dose
20 15 10
OR: 4.19 p=0.015
Grade 33 HEM toxicity
Grade 33 GI toxicity
Figure 1. Percentages of severe toxicity
Shown are the percentages of severe gastrointestinal and severe haematological toxicity of DPYD variant allele carriers with and without fluoropyrimidine dose reductions and wild-type patients in chemoradiation treatment.
Abbreviations: OR: adjusted odds ratio; DPYD: gene encoding dihydropyrimidine dehydrogenase; GI= gastrointestinal; HEM: haematological.
Included in Table 3 are any changes applied in chemotherapy during treatment due to ad- verse events, such as dose interruptions. Compared with wild-type patients, DPYD variant allele carriers had more dose reductions during treatment, stopped treatment prematurely and were hospitalised more often, regardless of any received dose reductions. However, the mean duration of hospitalisation of DPYD variant allele carriers who received a dose re- duction was notably shorter (4 days) compared with the DPYD variant allele carriers treated with a standard dose (23 days, p=0.010).
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Percentage
W ild-type + standard dose DPYD + standard dose
DPYD + reduced dose
W ild-type + standard dose DPYD + standard dose
DPYD + reduced dose