5-Fluorouracil (5-FU) is commercially available under several trade names, as Xeloda, Adrucil, Efudix, Carac, Fluoroblastin ... It is used in treatments of several kinds of cancers since about 50 years, nevertheless adverse reactions, and even lethal toxicity, have been described in approximately 30% of patients.
DNAVision has develops TherapID™: 5-FU test to help predict the patients who can suffer serious toxic reactions to this drug by the mean of their DNA. This new range of tests will allow to health care professionals adapt chemotherapy treatments to the patient needs.
TherapID™: 5-FU test is a simple test that analyzes the genetic variations in the DPYD gene in order to predict the risk for serious side effects in patient treated by 5-FU. This test will allow to improve 5-FU therapeutic effectiveness by the limitation of the side effects for the 1.5 millions of patients that are treated by 5-FU every year in the world.
DPYD enzymatic deficiency would be in the origin of nearly 8 % of the toxic reactions to 5-FU. Indeed, the enzyme coded by the DPYD gene is the primary responsible for metabolizing or breaking down 5-FU and clearing it from the body. A variation in this gene lead to a DPYD enzyme with a compromised activity, 5-FU is broken down more slowly and the body is exposed for a longer period of time to this chemotherapy agent.
Definitively, DPYD deficient patients can suffer serious toxic reactions that can lead to death when they are treated by 5-FU.
5-FU is a chemotherapy agent which belongs to the category of antimetabolites. Anitmetabolites are very similar to the substances that the cells normally use during its division but indeed when cells incorporate them, they are unable to divide.
5-FU is an antimetabolite specific of the S-phase of the cell cycle and leads to a lower cell proliferation and protein synthesis. It is used, for about 40 years, against cancers:
80% of 5-FU is catabolised in the liver by dihydropyrimidine dehydrogenase (DPD), producing inactive metabolites, which are eliminated through the lung and the kidney. Several studies have shown the influence DPYD gene polymorphisms on the efficacy and toxicity of 5-FU. DPD deficiency is associated with early and severe toxicity of 5-FU.
The most common 5-FU side effects, are diarrhea, nausea, mouth sores, taste changes, metallic taste in mouth, poor appetite and stomachache, watery eyes and low blood counts (white and red blood cells and platelets temporarily decease) and neuropathy.
About 10-29 % of patients receiving fluorouracil can suffer less common effects as skin reactions, hair thinning, nail changes and other serious adverse reactions.
Side effects are almost always reversible and will go away after the treatment is complete. Nevertheless, the kind of side effects and its severity depend on a variety of factors including dosage, individual’s metabolism (DPYD enzyme), other drugs given as part of a combination therapy and/or the schedule and duration of treatment. There are some options to help minimize or prevent them, as the TherapID™: 5-FU test developed by DNAVision s.a.