Impact of dose adjustment of fluoropyrimidines on toxicity in patients with DPD-deficient colorectal cancer: A single-center experience.

Abstract

94 Background: Fluoropyrimidines (FPs) are the chemotherapy backbone for most patients with CRC. FPs are metabolized by dihydropyrimidine dehydrogenase (DPD). Current guidelines recommend measuring DPD activity before chemotherapy administration to adjust the initial dose and thus prevent high-grade toxicity. However, the clinical impact of this strategy is still understudied. We aim to study the efficacy and toxicity of FPs dose modifications according to DPD activity in patients with CRC. Methods: We retrospectively identified all the CRC cancer patients treated with FPs between January 2017 and July 2021 and with DPD activity assessment at Hospital Universitario La Paz, Madrid, Spain. Clinical characteristics and tolerability were collected. Two cohorts were stablished according to its DPD activity, patients with a normal DPD metabolism (DPD wild-type patients) and patients with a diminished metabolism of FPs (DPD deficient patients). Results: A total of 249 CRC patients were included in this study. Sixteen patients (6,4%) were DPD deficient, and 15 of them (94%) received initially 50% of the recommended standard dosing of FPs (increasing to 75% in following cycles if well tolerated) according to guidelines. Forty percent of non-DPD deficiency started FPs at 75% of the standard initial dose due to frailty. Two toxic deaths were observed in the DPD-wild-type cohort, none in the DPD deficient cohort. Clinico-pathological characteristics of patients and their toxicity according to each cohort are depicted in the table. No significant differences in G3/4 toxicity between both groups (40% and 37% in the DPD-wild-type and DPD-deficient cohort, respectively). Diarrhea G3/4 was numerically more present in the DPD-deficient group (25% vs 12%, respectively). Conclusions: Overall, DPD genotype-guided FP treatment in DPD deficient patients with CRC may prevent high-grade toxicity. Diarrhea might still be higher in this group despite dose modifications, so careful surveillance and early treatment should be considered in these patients. [Table: see text]