First reported double drug–drug interaction in a cancer renal patient under everolimus treatment: therapeutic drug monitoring and review of literature

Everolimus is an inhibitor of mammalian target of rapamycin (mTOR) used in both transplantation and cancer treatment (breast, renal and neuroendocrine). In transplantation, therapeutic drug monitoring (TDM) is recommended due to the potential drug-drug interactions with chronic medications, which can affect everolimus pharmacokinetics. In cancer treatment, everolimus is used at higher doses than in transplantation and without a systematic drug monitoring.We present a case report of a 72-year-old woman with epilepsy history to whom everolimus 10 mg QD was prescribed as third line of treatment for renal cell carcinoma (RCC). The potential drug interactions between everolimus and the patient's chronic medications, carbamazepine and phenytoin, are significant as both are known as strong inducers CYP3A4 metabolism, potentially leading to underexposure to everolimus.TDM of everolimus was recommended by the pharmacist. The literature suggests that a minimum plasma concentration (Cminss) of everolimus over 10 ng/ml is associated with better response to treatment and progression-free survival (PFS). The patient's everolimus dose had to be increased until 10 mg BID, and regular monitoring of everolimus levels showed an increase in Cminss from 3.7 ng/ml to 10.8 ng/ml.This case highlights the importance of checking for potential drug interactions and monitoring everolimus levels in patients on chronic medication, especially those with several inducers or inhibitors of CYP3A4 metabolism. TDM can help to ensure that patients are treated with their optimal dose, which can improve the effectiveness of the treatment or minimize the risk of toxicities

Mobilization of Hematopoietic Stem Cells into Peripheral Blood for Autologous Transplantation Seems Less Efficacious in Poor Mobilizers with the Use of a Biosimilar of Filgrastim and Plerixafor: A Retrospective Comparative Analysis

Introduction: Biosimilars of granulocyte colony-stimulating factors (G-CSF) have shown similar efficacy to originator filgrastim (Neupogen® [NEU]; Amgen Inc.) as prophylaxis in neutropenia and in the mobilization of stem cells in patients receiving combination chemotherapy with G-CSF. Methods: This was a retrospective study in which the characteristics of stem cell mobilization treated with a G-CSF alone were compared in 216 patients and 56 donors. The two G-CSF compared were NEU and the biosimilar filgrastim Zarzio® (Sandoz GmbH) (referred to hereafter as BIO). Primary objectives were mobilization rate (minimum of 10 × 103/ml CD34+ on day 4 of treatment [day +4]) and use of the immunostimulant plerixafor (PLEX) in each group. Results: The general characteristics of the patients receiving NEU (n = 138) and those receiving BIO (n = 78) did not differ significantly. PLEX was used in 24% of BIO patients and in 25.7% of NEU patients. The median CD34+ cell count on day +4 was significantly lower in BIO patients who needed PLEX than in those who did not (2.4 vs. 4.8 × 103/ml; p = 0.002), as was the final CD34+ cell count (2.5 vs. 3.3 × 106/kg; p 0.03). Mobilization failure rate was higher in the BIO group than in the NEU group (20 vs. 0%; p = 0.01). With respect to donors, more than one apheresis was needed in three BIO donors, one of them with PLEX. The use of BIO was the only risk factor for mobilization failure in patients who needed PLEX (hazard ratio 10.3; 95% confidence interval 1.3-77.8). Conclusion: The study revealed that BIO had a lower efficacy for stem cell mobilization when the only treatment was G-CSF, especially in poor mobilizers needing PLEX

ICO-ICS Praxis para el tratamiento de la leucemia linfática crónica

Tractament mèdic; Tractament amb irradiació; Leucèmia limfàtica crònicaMedical treatment; Irradiation treatment; Chronic lymphocytic leukemiaTratamiento médico; Tratamiento con irradiación; Leucemia linfática crónicaLa leucèmia limfàtica crònica (LLC) és una alteració hematopoètica monoclonal caracteritzada per una expansió progressiva de limfòcits de la línia B. Aquests limfòcits, madurs des del punt de vista morfològic, però menys madurs des del punt de vista immunològic, s’acumulen a la sang, la medul·la òssia, els nòduls limfàtics i la melsa. Els principals objectius d’aquesta ICO-ICSPraxi són: - Desenvolupar, difondre, implementar i avaluar resultats de la ICO-ICSPraxi de la leucèmia limfàticacrònica (LLC). - Disminuir la variabilitat terapèutica entre els pacients tractats als diferents centres d'aquesta xarxa. - Implementar els resultats de la terapèutica en els pacients amb LLC tractats d'acord amb lesrecomanacions d'aquesta guia

ICO-ICS Praxi per al tractament mèdic i amb irradiació de càncer gàstric i d'unió esofagogàstrica

Tractament mèdic; Tractament amb irradiació; Càncer de la unió esofagogàstricaTratamiento médico; Tratamiento con irradiación; Cáncer de la unión esofagogástricaMedical treatment; Irradiation treatment; Esophagogastric union cancerEl càncer gàstric (CG) és actualment el vuitè tipus de càncer més prevalent a la Unió Europea on, segons les estimacions, el 2018 es calculen 80.211 casos diagnosticats en ambdós sexes amb una taxa estimada d'incidència estandarditzada per edat de 6,4 casos per cada 100.000 habitants. En el cas d'Espanya, segons dades d'incidència i mortalitat del projecte GLOBOCAN i de l'Observatori Europeu del Càncer, se situa en novè lloc, després del càncer de bufeta i el càncer uterí, pel que fa a freqüència. Els objectius d'aquesta guia són: Desenvolupar, difondre, implementar i avaluar resultats de l'ICO-ICSPraxi de càncer gàstric i d'unió esofagogàstrica. Disminuir la variabilitat terapèutica entre els pacients tractats als diferents centres d'aquesta institució. Implementar els resultats de la terapèutica en els pacients amb càncer gàstric i d'unió esofagogàstrica tractats d'acord amb les recomanacions d'aquesta guia.El cáncer gástrico (CG) es actualmente el octavo tipo de cáncer más prevalente en la Unión Europea donde, según las estimaciones, el 2018 se calculan 80.211 casos diagnosticados en ambos sexos con una tasa estimada de incidencia estandarizada por edad de 6,4 casos por cada 100.000 habitantes. En el caso de España, según datos de incidencia y mortalidad del proyecto GLOBOCAN y del Observatorio Europeo del Cáncer, se sitúa en noveno lugar, después del cáncer de vejiga y el cáncer uterino, en cuanto a frecuencia. Los objetivos de esta guía son: Desarrollar, difundir, implementar y evaluar resultados del ICO-ICSPraxi de cáncer gástrico y de unión esofagogástrica. Disminuir la variabilidad terapéutica entre los pacientes tratados en los diferentes centros de esta institución. Implementar los resultados de la terapéutica en los pacientes con cáncer gástrico y de unión esofagogástrica tratados de acuerdo con las recomendaciones de esta guía.Gastric cancer (GC) is currently the eighth most prevalent type of cancer in the European Union where, according to estimates, 80,211 cases diagnosed in both sexes are estimated at an estimated rate of incidence standardized by age of 6.4 cases per 100,000 people. In the case of Spain, according to the incidence and mortality data of the GLOBOCAN project and the European Cancer Observatory, it is placed ninth, after bladder cancer and uterine cancer, as it happens frequently. The objectives of this guide are: Developing, disseminating, implementing and evaluating the results of the ICO-ICSPraxi of gastric cancer and esophagogastric binding. Decrease the therapeutic variability between patients treated at the different centers of this institution. Implement the results of therapeutic treatment in patients with gastric cancer and esphagogastric binding treated in accordance with the recommendations of this guide

Flagellar membranes are rich in raft-forming phospholipids.

The observation that the membranes of flagella are enriched in sterols and sphingolipids has led to the hypothesis that flagella might be enriched in raft-forming lipids. However, a detailed lipidomic analysis of flagellar membranes is not available. Novel protocols to detach and isolate intact flagella from Trypanosoma brucei procyclic forms in combination with reverse-phase liquid chromatography high-resolution tandem mass spectrometry allowed us to determine the phospholipid composition of flagellar membranes relative to whole cells. Our analyses revealed that phosphatidylethanolamine, phosphatidylserine, ceramide and the sphingolipids inositol phosphorylceramide and sphingomyelin are enriched in flagella relative to whole cells. In contrast, phosphatidylcholine and phosphatidylinositol are strongly depleted in flagella. Within individual glycerophospholipid classes, we observed a preference for ether-type over diacyl-type molecular species in membranes of flagella. Our study provides direct evidence for a preferential presence of raft-forming phospholipids in flagellar membranes of T. brucei