Monitoring of the 5-FU therapy: Safety and efficacy of treatment?

Abstract

5-fluorouracil (5-FU) is one of the most common chemotherapeutics used in the therapy of cancers of the gastrointestinal tract, breast, skin or head and neck. The key enzyme of drug metabolism is encoded by DPYD dihydropyrimidine dehydrogenase (DPD), which is responsible for the catabolism of 80% of the administered 5-FU. Patients with DPD deficiency are exposed to a high risk of severe and sometimes lethal toxicity during treatment. Nonlinear pharmacokinetics and narrow therapeutic index significantly hinder the prediction of response of the body after administration of a standard dose. Therefore, the individual adjustment of the optimal dose enabling the best possible therapeutic effect with minimal side effects is very important. The commonly accepted method of adjusting 5-FU dose is based on the body surface area (BSA). Unfortunately, this does not allow us to determine the drug concentration ensuring the highest effectiveness of the treatment while maintaining its safety. Many publications point out the need of determining the activity of dihydropyrimidine dehydrogenase before the administration of 5-FU, which could result in obtaining the desired and optimal drug concentration in the blood, without exposing the patient to its excessive toxicity. Despite the great needs, such tests are not carried out routinely. Specification of procedures of DPD activity indication, determination of optimal 5-FU doses and monitoring of concentration of this chemotherapeutic during the treatment can become the basis for establishing some new therapeutic standards in the oncology, and in consequence, may significantly influence the quality and length of life of the patients.