Effectiveness, safety, and prognostic factors of trifluridine/tipiracil for the treatment of patients with metastatic colorectal cancer in routine clinical practice.

Background: The combination of trifluridine and tipiracil is indicated in patients with metastatic colorectal cancer previously treated or non-candidates to chemotherapy and biological therapies. This study in routine clinical practice aimed to describe the effectiveness and safety of trifluridine and tipiracil and identify prognostic factors in patients with metastatic colorectal cancer in Spain. Methods: This analysis was a retrospective, observational, multicenter study that included patients aged ≥18 years who had received treatment with trifluridine/tipiracil for metastatic colorectal cancer in third- or subsequent lines. Results: Overall, 294 were evaluated. Trifluridine/tipiracilmedian (minimum, maximum) treatment duration was 3.5 (1.0-29.0) months, and 128 (43.5%) patients received subsequent treatments. One hundred (34%) patients showed disease control rate, and the median progression-free survival and overall survival from trifluridine/tipiracil treatment onset were 3.7 and 7.5 months, respectively. The most frequently reported adverse events were asthenia (all grades, 57.9%) and neutropenia (all grades, 51.3%). A 39.1% and 4.4% of the participants had a dose reduction and a treatment interruption due to toxicity. Patients with age ≥65 years, low tumor burden, ≤2 metastasis sites, treatment dose reduction, neutropenia, and ≥6 cycles, had significantly higher overall survival, progression-free survival, and response rate. Conclusions: This real-life study indicates that trifluridine/tipiracil shows effectiveness and safety in treating patients with metastatic colorectal cancer. The results show a profile of metastatic colorectal cancer patients with previously unknown prognostic factors who have a more significant benefit from treatment with trifluridine/tipiracil in routine clinical practice.

Early use of tocilizumab in patients with severe pneumonia secondary to severe acute respiratory syndrome coronavirus 2 infection and poor prognostic criteria: Impact on mortality rate and intensive care unit admission.

ABSTRACT: The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2, keeps spreading globally. Evidence suggests that a subgroup of patients with severe symptomatology might have cytokine storms, which increases mortality. The use of interleukin-6 (IL-6) inhibitors may help in controlling the pathological immune response to the virus. Tocilizumab, a monoclonal antibody against IL-6, stands as an optional treatment for COVID-19 patients presenting this inflammatory hyper-response.We conducted a retrospective, observational, cohort study including 50 patients affected by COVID-19 with severe pneumonia and poor prognosis criteria, who have also undergone standard treatment; 36 of these patients additionally received tocilizumab in an early stage. The need for intensive care unit (ICU) admission, mortality, recovery of respiratory function, and improvement of biochemical and hematological parameters were compared between cohorts.Most patients were men, non-smokers and the most frequently reported comorbidities were hypertension and diabetes. Recurrent symptoms were fever, cough, and dyspnoea. 54.8% of patients from the tocilizumab group needed intubation, while in the control group 85.7% needed it. Treatment with tocilizumab significatively increased IL-6 levels, (554.45; CI 95% 186.69, 1032.93; P < .05) while C-reactive protein mean levels were reduced (-108.19; CI 95% -140.15, -75.33; P < .05), but no significant difference was found between cohorts. In comparison with the controls, tocilizumab reduced mortality (25.0% vs 42.9%, P = .021) and the number of ICU admissions (63.9% vs 100.0%, P = .021). 44.1% of patients treated with tocilizumab showed favorable radiological evolution, when compared with 15.4% of patients from the control group.Tocilizumab may improve clinical symptoms and mitigate deterioration observed in severe COVID-19 patients, and could be considered as an effective therapeutic option in subjects experiencing a significant inflammatory response to the disease.

Human Plasma Metabolomics for Biomarker Discovery: Targeting the Molecular Subtypes in Breast Cancer.

PURPOSE: The aim of this study is to identify differential metabolomic signatures in plasma samples of distinct subtypes of breast cancer patients that could be used in clinical practice as diagnostic biomarkers for these molecular phenotypes and to provide a more individualized and accurate therapeutic procedure. METHODS: Untargeted LC-HRMS metabolomics approach in positive and negative electrospray ionization mode was used to analyze plasma samples from LA, LB, HER2+ and TN breast cancer patients and healthy controls in order to determine specific metabolomic profiles through univariate and multivariate statistical data analysis. RESULTS: We tentatively identified altered metabolites displaying concentration variations among the four breast cancer molecular subtypes. We found a biomarker panel of 5 candidates in LA, 7 in LB, 5 in HER2 and 3 in TN that were able to discriminate each breast cancer subtype with a false discovery range corrected p-value < 0.05 and a fold-change cutoff value > 1.3. The model clinical value was evaluated with the AUROC, providing diagnostic capacities above 0.85. CONCLUSION: Our study identifies metabolic profiling differences in molecular phenotypes of breast cancer. This may represent a key step towards therapy improvement in personalized medicine and prioritization of tailored therapeutic intervention strategies.