Banca de DEFESA: ISLANIA ALMEIDA BRANDÃO BARBOSA

THE IMPORTANCE OF THERAPEUTIC MONITORING IN THE OCCURRENCE OF SERIOUS TOXICITY TO THE CHEMOTHERAPEUTIC FLUROURACIL IN PATIENTS WITH GASTROINTESTINAL NEOPLASIA

 

5-fluorouracil; toxicity; therapeutic monitoring; gastrointestinal cancer

Introduction: Cancer is the main public health problem in Brazil and worldwide, with emphasis on gastrointestinal cancer, which has a major association with environmental factors and lifestyle habits. The drug 5-fluorouracil is one of the main treatment alternatives for gastrointestinal cancers. The extremely short half-life, narrow therapeutic index, and inter-individual differences among patients lead to a limitation in its use due to the high possibility of occurrence of toxicities. Objective: This observational, longitudinal, retrospective, descriptive, uncontrolled single-center study aimed to assess the occurrence and severity of toxicities presented by patients using 5-fluorouracil medication and the importance of dose optimization and individualization. Methodology: The identification of the severity of 5-FU toxicities was based on the Common Toxicity Criteria, from the Common Terminology Criteria for Adverse Events (CTCAE) – version 5.0. Parametric ANOVA, non-parametric Kruskal-Wallis, and Chi-square (χ2) tests were used, in addition to the Mann-Whitney tests, in the statistical analysis of the data. Results and Discussion: Eighty-three patients undergoing treatment for colorectal cancer who underwent treatment with the FOLFOX protocol were evaluated (oxaliplatin 85 mg/m² IV in 2h of infusion; folinic acid 400 mg/m² IV in 2h of infusion; 5-FU 400 mg /m² in bolus; 5-FU 2400 mg/m² IV in 46 to 48 hours of infusion), between June 2020 and July 2021. The analyzes performed showed a higher frequency in males of developing toxicity, with hematological toxicities being more frequent in both sexes, in addition to presenting with greater severity. In addition, 44.6% of patients did not complete the proposed treatment, with disease progression being the main cause. Interferences in treatment due to adverse events to 5-FU were reported 112 times, leading to delay, temporary discontinuation of treatment (with or without hospitalization), complete discontinuation, and/or dose adjustment. BMI and development of severe toxicities were significantly dependent (p = 0.000). Conclusion: The results suggest a strong association between the presented toxicities and the need to suspend treatment and/or dose adjustments with a possible reduction in therapeutic efficacy and increase in healthcare costs. This study demonstrates the need for individualized treatment with more adequate management of adverse events.