5-fluorouracil therapeutic drug monitoring and adverse events in a Romanian population.

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.

Recurrent cardiotoxicity in a fluoropyrimidine treated cancer patient - case report and practical recommendations.

Fluoropyrimidines remain some of the most used chemotherapeutics, despite the appearance in the therapeutic arsenal of targeted therapy and immunotherapy. Fluropyrimidines related cardiotoxicity is an undesirable adverse event and affects almost 20% of patients. The mechanisms of fluoropyrimidine toxicity are closely related to deficient allelic variants of DPYD, but considering the low penetrance and interindividual variability, not all adverse reactions are explained by their presence. In this case, we report a patient with recurrent fluoropyrimidine toxicity without a deficient allelic variant and how this case was managed by the oncologist and cardiologist, considering the need to use fluoropyrimidine in the treatment.

Multiple potential targets of opioids in the treatment of acute respiratory distress syndrome from COVID-19.

COVID-19 can present with a variety of clinical features, ranging from asymptomatic or mild respiratory symptoms to fulminant acute respiratory distress syndrome (ARDS) depending on the host's immune responses and the extent of the associated pathologies. This implies that several measures need to be taken to limit severely impairing symptoms caused by viral-induced pathology in vital organs. Opioids are most exploited for their analgesic effects but their usage in the palliation of dyspnoea, immunomodulation and lysosomotropism may represent potential usages of opioids in COVID-19. Here, we describe the mechanisms involved in each of these potential usages, highlighting the benefits of using opioids in the treatment of ARDS from SARS-CoV-2 infection.

A review on the importance of genotyping and phenotyping in fluoropyrimidine treatment.

Fluoropyrimidines, after more than 50 years from their discovery, are still the treatment of many types of cancer, and it is estimated that two million patients receive fluoropyrimidine therapy annually. 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. This is an important reason to determine DPD activity in order to improve patient safety and to limit potential life-threating toxicity. At presentmultiple phenotypic and genotypic methods are available for the determination of DPD activity, some of these methods have proven their usefulness in practice, and yet they are not routinely recommended in clinical practice. This review is another statement of the importance of the determination of DPD status, the phenotypic and genotypic methods that are available and can be used.

Fluoropyrimidine-induced cardiotoxicity.

Cardio-oncology is a discipline based on early screening, monitoring, and treating chemotherapy-induced cardiotoxicity. There are many chemotherapeutics known for their cardiac toxic effects, including fluoropyrimidines. Fluoropyrimidine represents the cornerstone of many types of cancer and each year almost two million cancer patients undergo this treatment. Fluoropyrimidine-induced cardiotoxicity can be manifested in several forms, from angina pectoris to sudden death. This paper is a review of how the cardiotoxicity of fluoropyrimidines is presented, the mechanisms of its occurrence, its diagnosis, and management.

IL-6 roles - Molecular pathway and clinical implication in pancreatic cancer - A systemic review.

Pancreatic cancer has attracted a great deal of attention owing to the poor outcome, increasing prevalence in the last years and delay diagnosis. Known as a complex disease, it involves genetic mutations, changes in tumour microenvironment and inflammatory component dominated by interleukin-6 and its activated pathways, like Janus Kinase-Signal Transducer and Activator of Translation3, Mitogen Activated Protein Kinase and Androgen receptor. The pro-inflammatory cytokine, plays a central role in oncogenesis, cancer progression, invasiveness, microenvironment changes, treatment resistance, prognosis and associated co morbidities like cachexia and depression. Fulfilling these roles IL-6 requires special attention to understand its complexity in PC development.