Tailored therapy in patients treated with fluoropyrimidines: focus on the role of dihydropyrimidine dehydrogenase  

作　　者：Filippo Merloni Nicoletta Ranallo Laura Scortichini Riccardo Giampieri Rossana Berardi 

机构地区：[1]Scuola di Specializzazione in Oncologia,Universita Politecnica delle Marche,Ancona 60121,Italy [2]Clinica Oncologica,UniversitàPolitecnica delle Marche,AOU Ospedali Riuniti,Ancona 60126,Italy

出　　处：《Cancer Drug Resistance》2019年第3期787-802,共16页癌症耐药（英文）

摘　　要：Fluoropyrimidines are widely used in the treatment of solid tumors, mainly gastrointestinal, head and neck and breast cancer. Dihydropyrimidine dehydrogenase (DPD) is the rate-limiting enzyme for catabolism of 5-FU and it is encoded by DPYD gene. To date, many known polymorphisms cause DPD deficiency and subsequent increase of 5-FU toxicity. In addition, reduced inactivation of 5-FU could lead to increased 5-FU intracellular concentration and augmented efficacy of this drugs. Therefore DPD expression, particularly intratumoral, has been investigated as predictive and prognostic marker in 5-FU treated patients. There also seems to be a tendency to support the correlation between DPD expression and response/survival in patients treated with fluoropyrimidine even if definitive conclusions cannot be drawn considering that some studies are conflicting. Therefore, the debate on intratumoral DPD expression as a potential predictor and prognostic marker in patients treated with fluoropyrimidines is still open. Four DPD-polymorphisms are the most relevant for their frequency in population and clinical relevance. Many studies demonstrate that treating a carrier of one of these polymorphisms with a full dose of fluoropyrimidine can expose patient to a severe, even life-threatening, toxicity. Severe toxicity is reduced if this kind of patients received a dose-adjustment after being genotyped. CPIC (Clinical Pharmacogenetics Implementation Consortium) is an International Consortium creating guidelines for facilitating use of pharmacogenetic tests for patient care and helps clinicians ensuring a safer drug delivery to the patient. Using predictive DPD deficiency tests in patients receiving 5FU-based chemotherapy, in particular for colorectal cancer, has proven to be a cost-effective strategy.

关 键 词：5-FLUOROURACIL FLUOROPYRIMIDINES CHEMOTHERAPY dihydropyrimidine dehydrogenase dihydropyrimidine dehydrogenase DPYD CPIC POLYMORPHISMS 

分 类 号：R73[医药卫生—肿瘤]