Abstract
5-Fluorouracil (5-FU) and oral fluoropyrimidines, such as capecitabine, are widely used in the treatment of cancer, especially gastrointestinal tumors and breast cancer, but their administration can produce serious and even lethal toxicity. This toxicity is often related to the partial or complete deficiency of the dihydropyrimidine dehydrogenase (DPD) enzyme, which causes a reduction in clearance and a longer half-life of 5-FU. It is advisable to determine if a DPD deficiency exists before administering these drugs by genotyping DPYD gene polymorphisms. The objective of this consensus of experts, in which representatives from the Spanish Pharmacogenetics and Pharmacogenomics Society and the Spanish Society of Medical Oncology participated, is to establish clear recommendations for the implementation of genotype and/or phenotype testing for DPD deficiency in patients who are candidates to receive fluoropyrimidines. The genotyping of DPYD previous to treatment classifies individuals as normal, intermediate, or poor metabolizers. Normal metabolizers do not require changes in the initial dose, intermediate metabolizers should start treatment with fluoropyrimidines at doses reduced to 50%, and poor metabolizers are contraindicated for fluoropyrimidines.
Highlights
Fluoropyrimidines or dihydropyrimidines (5-fluorouracil [5-FU], capecitabine, and tegafur) are antimetabolite drugs that are widely used to treat solid tumors, including breast and colorectal cancers and other gastrointestinal tract cancers
10–40% of patients treated with fluoropyrimidines develop severe toxicity, which may include myelosuppression, severe diarrhea, vomiting, stomatitis, mucositis, hand–foot
The phenotype of dihydropyrimidine dehydrogenase (DPD) can be defined by the presence or absence of singlenucleotide polymorphisms (SNPs) in the DPYD gene that alter the activity of the DPD enzyme
Summary
Abstract 5-Fluorouracil (5-FU) and oral fluoropyrimidines, such as capecitabine, are widely used in the treatment of cancer, especially gastrointestinal tumors and breast cancer, but their administration can produce serious and even lethal toxicity. This toxicity is often related to the partial or complete deficiency of the dihydropyrimidine dehydrogenase (DPD) enzyme, which causes a reduction in clearance and a longer half-life of 5-FU. It is advisable to determine if a DPD deficiency exists before administering these drugs by genotyping DPYD gene polymorphisms.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have