Detecting a dihydropyrimidine dehydrogenase (DPD) deficiency with validated screening tests before starting cancer treatment can contribute to a reduction in the toxicity of fluoropyrimidines.
In France, the National Cancer Institute (Institut national du cancer - INCa) and the Higher Health Authority (Haute Autorité de Santé - HAS) have published recommendations for the detection of a dihydropyrimidine dehydrogenase (DPD)-deficiency within the framework of chemotherapy with fluoropyrimidines. In order to detect this deficiency, the HAS recommends the following:
- detection of a DPD deficiency before starting each cycle of 5-fluorouracil (%-FU) or capecitabine;
- performing screening via phenotyping by, in the first instance, determining the quantity of plasma uracil (U) (possibly with the supplement of the ratio of dihydrouracil (UH2/U) and combining this with the genotyping of the variants *2A, *13, p.D949V and HapB3.
- if necessary, reducing the dose of the first cycle, in function of DPD status, and considering an increase in the dose of the subsequent cycles depending on the dose tolerated by the patient (Feb 18, 2018 - ANSM and December 2018 - INCa).
In Belgium, the genotyping test for mutations of the dihydropyrimidine dehydrogenase gene (DPYD) (sequence determination of 9 of the 23 exons, including detection of the 4 recommended polymorphisms) is currently a routine test carried out in laboratories of university hospitals. This test is included in the limitive list of centres for anthropogenetics and is reimbursed by the National Institute for Health and Disability Insurance (RIZIV).
Currently laboratories in Belgium are working on the development for a DPD phenotyping tests by measuring U and UH2.
The use of these tests before starting treatment can help to reduce the toxicity of fluoropyrimidines. This toxicity is a real problem for public health: this can affect the quality of life of the patient, require an interruption or discontinuation of the cancer treatment and even put the life expectancy of the sick people at risk.
Available specialities in Belgium
- 5-fluorouracil: FLURACEDYL® and FLUOROURACIL ACCORD HEALTHCARE®
- Capecitabine: XELODA®, CAPECITABINE ACCORD® and CAPECITABINE EG®