Fluoropyrimidines, after more than 50 years of their discovery, are still the treatment of many types of cancer, and annually is estimated that two million patients use fluoropyrimidine treatment. The toxicity associated with fluoropyrimidines affects 30-40% of patients and some adverse effects can be lethal. Dihydroypyrimidine dehydrogenase is the main enzyme in the catabolism of 5-FU and DPD activity deficiency can cause important toxicity. There is an important reason for determinate DPD activity in order to improve patient safety and to limit potential life-threating toxicity. Now, are available multiple phenotypic and genotypic methods to determinate DPD activity, some of this methods have proven their usefulness in practice, but yet there are not routinely recommended in clinical practice. This review is another statement of the importance of determination DPD status, the phenotypic and genotypic methods that are available and can be used.
Fluoropyrimidines represent the backbone of many chemotherapy protocols and the standard treatment for many types of tumors. Toxicity associated with fluoropyrimidines can occur in up to 40% of cases. Background and purpose. The objective of this study was to analyze the correlation between the plasma concentration of 5-fluorouracil and the adverse events that patients might experience during this therapy. Methods. A total of 58 patients received 5-fluorouracil-based chemotherapy. A blood sample was collected from each patient during the drug infusion, in order to assess the area under the curve for 5-fluorouracil. The occurring adverse events were evaluated through medical recordings of the patients’ reported symptoms, clinical and paraclinical examinations. Results. In our study, the majority of patients experienced some type of toxicity. Moreover, we found a correlation between 5-FU plasma concentration (expressed as AUC) and adverse events, a stronger one with hematological adverse reactions and a weaker one with gastrointestinal and cardiovascular toxicity. Conclusion. Determining the plasma concentration of 5-FU in patients with severe toxicities could represent a method of individualizing the treatment and improving the safety profile.
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