5PSQ-061 Determination of genetic polymorphisms of the dihydropyrimidine dehydrogenase gene in real clinical practice: posological individualisation

• Published in: European journal of hospital pharmacy. Science and practice Vol. 26; no. Suppl 1; pp. A229 - A230
• Main Authors: Alvarado Fernández, MD, Murillo Izquierdo, M, Cordero Ramos, J, Rendón de Lope, L, Rengifo, MDLCDonoso, Moya Martin, ML
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group LTD 01.03.2019
• Subjects: Colorectal cancer; Dehydrogenases; Drug dosages; Enzymes; Gastric cancer; Head & neck cancer; Pancreatic cancer; Patients; Tumors
• ISSN: 2047-9956; 2047-9964
• DOI: 10.1136/ejhpharm-2019-eahpconf.494

BackgroundFluoropyrimidines are antineoplastic drugs used for the treatment of many types of solid tumours. Approximately 80%–90% administered are metabolised by the enzyme dihydropyrimidine dehydrogenase (DPYD).The partial or total deficiency of this enzyme is related to severe toxicity and, in some cases, it can cause the death of the patient.PurposeThe aim of our study was to determine the frequency of these polymorphisms in the DPYD gene in patients treated in our hospital and identify those patients with a predisposition to excessive toxicity if they are exposed to fluoropyrimidines.Material and methodsThe genetic analysis of the DPYD gene was performed on all patients who started treatment with fluoropyrimidines between September 2017 and June 2018. The variables collected were: sex, age, type of tumour diagnosed and toxicity presented in the first five treatment cycles according to the Common Terminology Criteria for Adverse Events (CTCAE) classification. Data was obtained by the electronic medical record (Diraya) and the electronic prescription program (Farmis).The polymorphisms studied were rs3918290, rs55886062, rs67376798 and rs56038477 (evidence 1A).ResultsThe genetic analysis was performed on 89 patients, 76% males and 24% females. The median age was 70 years.Most of the diagnoses corresponded to colorectal cancer (81%), 13% gastric tumours, 3% pancreatic tumours and 3% tumours of the head and neck. The patients presented the following adverse events: digestive toxicity in 57% of patients (CTCAE: 1, 2, 3), haematological toxicity 15% (CTCAE: 2), hepatotoxicity 6% (CTCAE: 2, 3), neuropathy 16% (CTCAE: 1, 2) and erythrodysaesthaesia 10% (CTCAE: 1, 2, 3).Thirty-seven per cent of patients required drug withdrawal or dose reduction due to the toxicity presented.Regarding the results of the polymorphisms studied, 97% presented a wild-type genotype for the analysed variants. Three per cent of patients presented some mutated allele (heterozygote): one patient for rs3918290 and two patients for rs67376798, coinciding with the patients who presented greater toxicity.ConclusionThe heterozygous patients detected are at risk of developing severe toxicity when they are treated with fluoropyrimidines and they required a dose adjustment of these drugs.The use of these pharmacogenetic tools for the determination of polymorphisms of the DPYD gene in routine practice allows us to predict the potentially serious toxicity favouring the individualised use of these drugs.References and/or acknowledgementsNone.No conflict of interest.