Association between genetic polymorphisms of dihydropyrimidine dehydrogenase enzymes and adverse effects in pacients treated with capecitabine

• Grant number: 18/09306-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: September 01, 2018
• End date: February 15, 2020
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Patricia Moriel
• Grantee: Mariana Real Bispo Medeiros
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Capecitabine (CAPE), a prodrug of 5-fluorouracil (5-FU), is widely adopted in clinical practice as a chemotherapeutic agent incorporated in the treatment of several malignancies such as colorectal and gastric cancer and is available on SUS. Although it has shown benefits in patient survival, its incidence of serious adverse events are very significant ,mostly gastrointestinal, dermatologic and constitutional effects are seen, which can affect the treatment efficiency. In spite of the fact that many non genetic causes can affect the efficiency of the medication, such as age, diseases and drug-drug interactions there meaningful cases which interindividual differences to the same treatment is caused by polymorphic genes that codifies drug-metabolizing enzymes, drug transporters and targets leading to excessive toxicity or inefficiency. When it comes to capecitabine, several studies give prominence to polymorphisms of DYPD, that encodes dihydropyrimidine dehydrogenase (DPD) enzyme responsible for 80% degradation of the administered dose of 5-FU. DPD deficiency is detected on 39-61% of pacientes with severe toxicity. The present study aims to characterize patients under treatment of capecitabine and relation with the occurrence of polymorphism in DPYD*5 (rs1801159) and adverse effects caused by the treatment. It will be a longitudinal and observational study conducted on the oncology clinic of Hospital de Clínicas/UNICAMP.