Pharmacokinetic Individualization of 5-Fluorouracil Doses in Colorectal Cancer

• Autor(a) principal: Martins, Carina Gomes
• Data de Publicação: 2013
• Outros Autores: Wagner, Sandrine Comparsi, Linden, Rafael
• Tipo de documento: Artigo
• Idioma: por
• Título da fonte: Revista Brasileira de Cancerologia (Online)
• Texto Completo: https://rbc.inca.gov.br/index.php/revista/article/view/535
• topic: Neoplasias Colorretais; Famacocinética; Antineoplásicos-uso terapêutico; Antineoplásicos-efeitos adversos; Quimioterapia; Colorectal Neoplasms; Pharmacokinetics; Antineoplastc Agents-therapeutic use; Antineoplastc Agents –adverse effects; Drug Therapy; Neoplasias ColorrectalesFamacocinética; Antineoplásicos-uso terapéutico; Antineoplásicos-efctos adversos; Quimioterapia

Introduction: 5-FU is an antimetabolite widely used in the treatment of colorectal cancer, presenting a significant interindividual variability in both therapeutic response and occurrence of toxicity, which may be attributed to its variable pharmacokinetics. Objectives: The purpose of this study is to review the clinical and laboratory aspects of the pharmacokinetic individualization of 5-FU dose regimens in colorectal cancer. Method: It was performed a bibliographic search on the databases PubMed, Periodicals Capes, SciElo, Medline and Bireme, including studies published since 1997. Search key-words were 5-Fluorouracil; Pharmacokinetic individualization; Colorectal cancer; Therapeutic drug monitoring, both in English and Portuguese. Results: There are evidences of a relationship between the systemic exposure to 5-FU and treatment responses, with an area under the concentration-time curve of 20- 25 mg.h/L representing a compromise between efficacy maximization and toxicity reduction. It is also possible to evaluate the DPD enzyme activity prior to 5-FU treatment through phenotypic methods, identifying patients at risk of severe toxicity. Analytical methods based on high performance liquid chromatography are available to measure 5-FU concentrations in plasma, allowing the dissemination of therapeutic drug monitoring in 5-FU treatments. Conclusion: Pharmacokinetics individualization allows the tailoring of personalized 5-FU therapeutic regimens in colorectal cancer, with significant impacts on the results of the therapy.