Dihydropyrimidine dehydrogenase deficiency frequency and its impact on 5-fluorouracil (5-FU) based chemotherapy toxicity

5-fluorouracil (5-FU) and its prodrug capecitabine are Fluoropyrimidines, widely used in colorectal cancer. The prevention of adverse effects related to severe toxicity of Fluoropyrimidines essentially involves pre-therapeutic screening for dihydropyrimidine dehydrogenase (DPD) deficiency, which must be carried out systematically before starting treatment with fluorouracil or capecitabine since the joint HAS/INCa recommendations of December 2018. The objective of our study is to assess the frequency of DPD deficiency and its impact on the occurrence of toxicities related to DPD deficiency.

We carried out a retrospective study on the files of patients treated, during the year 2022 and 2023, for colorectal cancer by chemotherapy and/or targeted therapy in an adjuvant and palliative situation based on 5-fluorouracil (5-FU) and its prodrug capecitabine, at the level of the Medical Oncology department of the CHU Tlemcen.

We collected 100 patients. Sex ratio 0.7, the average age was 58 years. All patients were treated with chemotherapy, for localized disease in 68 patients (68%), locally advanced in 04 patients (4%) and metastatic in 27 patients (27%). Liver metastases were found in 20 patients. The phenotypic assay of DPD within the pre-therapeutic tests was carried out in 90 patients (90%). A partial deficiency was found in 11 patients (12%) motivating a reduction to 2/3 of the doses. Despite this reduction, toxicity was noted in 09 patients (10%) with type of gastrointestinal toxicity in 06 patients, no reduction or discontinuation of treatment was recommended. For 79 patients without DPD deficiency (87%), 73 patients (92%) reported toxicity mainly gastrointestinal type in 55 patients (61%), cutaneous 23 patients (25%) and hematological 11 patients (12%). Asthenia was found in 31 patients (34%). The treatment was modified by dose reduction in 20 patients (24%) and stopped in 5 patients (6%) following serious toxicities: two episodes of grade IV hand-foot syndrome in 03 patients, and an acute coronary syndrome in 02 patients There was an increased risk of toxicity (grade 3 and 4) in patients with liver metastases despite the absence of DPD deficiency

The search for DPD deficiency by phenotypic study allows adaptation of the 5 FU doses to avoid major toxicity. However, other parameters may also have a role in the occurrence of toxicity, namely the deterioration of liver function and the cardiac impact of drugs.

The authors.

Has not received any funding.

All authors have declared no conflicts of interest.