527P - Systematic detection of dihydropyrimidine dehydrogenase (DPD) deficiency using UH2/U ratio in patients with digestive cancers in central Tunisia: Toxicity profile

Background

Fluoropyrimidines (FP), are recognized as effective medications for gastrointestinal tumors and have been in use for an extended period. The DPD enzyme is the primary catalyst responsible for eliminating 5-FU. The deficiency of this enzyme can result in various degrees of toxicity potentially leading to fatal polyvisceral failure.

Methods

A retrospective study involving patients treated for digestive cancers with an indication for FP-based chemotherapy who were systematically screened for DPD activity at the Department of Oncology at Farhat Hached Sousse from January 2019 to December 2021 by calculating UH2/U ratio (R). 2 groups were defined: Group 1 : R >=1.5 : Normal DPD activity Group2 : R <1,5 : Reduced DPD activity.

Results

We included 265 patients: 228 patients had normal DPD activity (86 %) and 37 had DPD deficiency (14 %), which was partial in 12.5%, severe in 1,5 %. In the first group overall chemotherapy toxicity was observed in 75.2 % of patients, and appeared early (1^st, 2^nd cycles) in 79,4 % of cases. Severe toxicities were observed in 17.1% of cases. Digestive toxicities, were the most frequent in this group (49,5%), and were grade 1 in 55.7% of cases. 36.6% of patients experienced hematological toxicity, predominantly grade 3or 4, with neutropenia being the most prevalent (28.6%), followed by thrombocytopenia (10.6%) and anemia (4.1%). Tragically, there were 2 toxic deaths reported. In the 2^nd Group, after dose adjustments, including a 50% reduction in continuous 5FU doses with bolus suppression, overall chemotherapy toxicity was reduced compared to the first group (61.1% vs. 75.2%). These adverse effects manifested early in 95.2% of cases. No severe toxicity was observed in this group, with all toxicities manageable at grade 1 or 2. Although the frequency of hematological toxicities was slightly reduced (32.3% vs. 36.6%), there was a notable increase in digestive adverse effects, particularly diarrhea (25.8%). Additionally, no instances of cardiac toxicity or toxic deaths were reported in this group.

Conclusions

Our study showed that systematic screening for DPD activity by using UH2/U ratio could reduce the severe toxicity of FP-based chemotherapy.

Legal entity responsible for the study

Medical Oncology Department Sousse.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.