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.

Pathological complete response following cisplatin or carboplatin-based neoadjuvant chemotherapy for triple-negative breast cancer: A systematic review and meta-analysis.

The addition of platinum compounds to standard neoadjuvant chemotherapy (NACT) for triple-negative breast cancer (TNBC) is highly controversial. Platinum agents, such as cisplatin and carboplatin, are DNA-damaging agents which exhibit activity in breast cancer, particularly in the TNBC subgroup. In order to assess the efficacy of each most representative platinum agent (cisplatin and carboplatin) in patients with TNBC treated with NACT, the present study performed a systematic review and meta-analysis of all available published studies on TNBC. A search of PubMed was performed to identify studies that investigated platinum-based NACT in patients with TNBC. The primary endpoints were the pooled rate of the pathological complete response (pCR) between cisplatin vs. carboplatin-based NACT. A total of 24 studies were selected (17 studies for carboplatin and 6 studies for cisplatin and 1 study with both carboplatin and cisplatin, with 20 prospective studies) for the analysis of 1,711 patients with TNBC. Overall, the pooled rate of pCR in patients treated with platinum-based NACT was 48%. No significant differences were observed between the rates of pCR obtained under carboplatin vs cisplatin treatment. The carboplatin pCR rate was 0.470 [95% confidence interval (CI), 0.401-0.539], while the cisplatin pCR rate was 0.473 (95% CI, 0.379-0.568). The comparison between these two categories revealed no significant differences (P=0.959). In the whole, the present study demonstrates that neoadjuvant platinum-based chemotherapy improves the pCR rate in patients with TNBC, regardless of the platinum agent used. Carboplatin may thus represent a viable option due to its more favorable toxicity profile.

Decrease of oncological patients' hospital visits during Covid-19 pandemic; the experience of a tertiary Romanian centre.

PURPOSE: The outbreak of COVID-19 pandemic has changed the provision of medical services worldwide. We assessed the impact of the pandemic on the oncological patients' visits to a tertiary cancer centre. METHODS: We analysed registrations from the administrative data system of in- and outpatients in all of the departments of the Cluj-Napoca Oncology Institute, during March-October 2020, and compared to the same 7-month period of the previous year. RESULTS: The decrease during March-October 2020 was 40.2% for new referrals overall (with the most significant drop in April, of 80%), 52.5% for medical oncology inpatients, 39% for paediatric oncology department inpatients, 69% for radiotherapy inpatients, 34.9% for surgical interventions and 31% decrease of issued pathology reports. The decrease was less important for outpatients: only 10% for medical oncology outpatient department, 33% for radiotherapy and 27% for breast cancer unit outpatients. Imaging investigations were only slightly influenced by the pandemic (reduction of 5% for MRI scans, 19% for mammograms,whereas performed CT scans were even more after the outbreak of COVID-19). CONCLUSION: Our results show a decrease in the number of patients during the period after the outbreak of the COVID-19 pandemic, more for inpatients and less significant for outpatient departments, probably because of the internal circuits reorganization but also because of health care measures taken nationally and locally to limit the spread of the pandemic.

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.