Abstract 526P
Background
Fluoropyrimidines are metabolized in the liver by the enzyme dihydropyrimidine dehydrogenase (DPD), encoded by the DPYD gene. About 7% of the European population is a carrier of DPYD gene polymorphisms associated with reduced DPD enzyme activity. The aims of the present retrospective analysis are: 1) to assess the prevalence of DPYD gene polymorphisms in a real world series of Italian patients with gastrointestinal malignancies; 2) to evaluate the impact of the DPYD testing on the frequency of severe toxicities, fluoropyrimidine dose reduction, and treatment delay.
Methods
300 consecutive patients with a diagnosis of gastrointestinal malignancy and treated with a fluoropyrimidine-based regimen are included in the analysis and divided in two cohorts: A) including 149 patients who started fluoropyrimidines after DPYD testing; B) including 151 patients treated without DPYD testing. Among the patients in cohort A, 15% tested only the DPYD*2A polymorphism, 19% tested four polymorphisms (DPYD*2A, HapB3, c.2846A>T and DPYD*13) and 66% tested five polymorphisms, including DPYD*6.
Results
Overall, 14.8% of patients resulted to be carriers of a DPYD variant, the most common being DPYD*6 (12.1%). Patients in cohort A reported fewer ≥ G3 toxicities (p = 0.00098), particularly fewer non-haematological toxicities (p = 0.0028) as compared with cohort B, while there was no statistically significant difference between the two cohorts in haematological toxicities (p = 0.6944). Significantly fewer chemotherapy dose reductions (p = 0.00002) were detected in cohort A with respect to cohort B, while there was no statistically significant difference in chemotherapy delay (p = 0.09136).
Conclusions
Although the sample size is limited and the analysis is retrospective, it provides additional information on the prevalence of DPYD polymorphisms in the Italian population and highlights the role of pharmacogenetic testing prior to treatment with fluoropyrimidines, in order to spare severe toxicity.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.