DPYD variant testing in candidates for fluoropyrimidine treatment: A study protocol

The main purpose of this study is to evaluate the potential clinical impact of pharmacogenetic testing on the reduction of the toxicity in patients treated with fluoropyrimidines. This will be achieved by  comparing the frequency of adverse events and the incidence of toxicity of two groups of patients that will differ from each other only in that one  will receive pharmacogenetic counseling. The hypothesis is that availability of a pharmacogenetic report prior to treatment initiation has a positive  effect. One of the main secondary goals is to analyze allele frequencies  and the association of polymorphisms rs895819 (miR27A) and rs1801160  (DPYD*6) with toxicity by conducting an observational study to determine  their clinical relevance and standardize a dose adjustment  recommendation.

The study has an single-center ambispective, quasi-experimental design and is based on a multidisciplinary protocol involving  implementation and standardization of DPYD*2A; DPYD*13; c.2846A>T;  and HapB3 measurements. Following these measurements,  pharmacogenetic counseling will be carried out and its clinical impact will  be evaluated. The primary endpoint of the study is severe toxicity and/or  mortality. The toxicity observed in two groups with similar epidemiological  characteristics will be compared: the intervention group (candidates for  treatment with fluoropyrimidines who will be subjected to the protocol)  and the control group (retrospective cohort). Additionally, rs895819  (MIR27A) and rs1801160 (DPYD*6) will be determined. Testing for these  variants is not part of the hospital's daily practice, nor are they included in  clinical guidelines. However, according to recently published studies, the  activity of dihydropyrimidine dehydrogenase might be affected by these  variants, as they may be associated with toxicity. The results of the  measurements of these two variants will not be incorporated to  pharmacogenetics counseling until their association with toxicity is  determined by means of the observational study to be conducted. The  project, as well as the patient information sheet and the informed consent  form, were approved by the Ethics Committee of the participating center  (code 20/006).