Search results for "Everolimu"

Management of toxicities associated with targeted therapies for HR-positive metastatic breast cancer: a multidisciplinary approach is the key to succ…

2019

Purpose: Agents targeting HR-positive, HER2-negative locally advanced or metastatic breast cancer have improved patient outcomes compared with conventional single-agent endocrine therapy. Currently, approved targeted agents include everolimus and three CDK4/6 inhibitors, palbociclib, ribociclib, and abemaciclib. Unlike the well-characterized and easily manageable safety profile of endocrine therapies, adverse events associated with targeted therapies are complex and potentially severe. Their prompt recognition and treatment, crucial for prolonged endocrine sensitivity and survival, may be challenging and requires a multidisciplinary effort and a good knowledge of drug interactions. Methods:…

2020

Progressive bladder cancer growth is associated with abnormal activation of the mammalian target of the rapamycin (mTOR) pathway, but treatment with an mTOR inhibitor has not been as effective as expected. Rather, resistance develops under chronic drug use, prompting many patients to lower their relapse risk by turning to natural, plant-derived products. The present study was designed to evaluate whether the natural compound, sulforaphane (SFN), combined with the mTOR inhibitor everolimus, could block the growth and proliferation of bladder cancer cells in the short- and long-term. The bladder cancer cell lines RT112, UMUC3, and TCCSUP were exposed short- (24 h) or long-term (8 weeks) to ev…

PTEN status is a crucial determinant of the functional outcome of combined MEK and mTOR inhibition in cancer

2017

AbstractCombined MAPK/PI3K pathway inhibition represents an attractive, albeit toxic, therapeutic strategy in oncology. Since PTEN lies at the intersection of these two pathways, we investigated whether PTEN status determines the functional response to combined pathway inhibition. PTEN (gene, mRNA, and protein) status was extensively characterized in a panel of cancer cell lines and combined MEK/mTOR inhibition displayed highly synergistic pharmacologic interactions almost exclusively in PTEN-loss models. Genetic manipulation of PTEN status confirmed a mechanistic role for PTEN in determining the functional outcome of combined pathway blockade. Proteomic analysis showed greater phosphoprote…

Efficacy and safety of everolimus in extrapancreatic neuroendocrine tumor: a comprehensive review of literature

2016

BACKGROUND Everolimus, an oral mTOR (mammalian target of rapamycin) inhibitor, is currently approved for the treatment of progressive pancreatic neuroendocrine tumors (NETs). Although promising, only scattered data, often from nondedicated studies, are available for extrapancreatic NETs. PATIENTS AND METHODS A systematic review of the published data was performed concerning the use of everolimus in extrapancreatic NET, with the aim of summarizing the current knowledge on its efficacy and tolerability. Moreover, the usefulness of everolimus was evaluated according to the different sites of the primary. RESULTS The present study included 22 different publications, including 874 patients and 4…

Analysis of everolimus starting dose as prognostic marker in HR+ mBC patients treated with everolimus (EVE) + exemestane (EXE): Results of the 3rd in…

2017

1061 Background: BRAWO is a German non-interventional study, which enrolled more than 2400 patients (pts) with advanced/metastatic, hormone-receptor-positive and HER2-negative breast cancer treated with EVE and EXE. Main objectives are a) the impact of physical activity on efficacy and quality of life, b) prophylaxis and management of stomatitis in clinical routine, and c) the sequence of therapy when EVE is used in daily clinical practice. Methods: In this update on the results of the 3rd interim analysis (data cut-off 18-Oct-2016) we analyzed under real world conditions the first 1.078 patients followed up until disease progression for their progression-free survival (PFS) events. A two-…

Compassionate use of everolimus for refractory epilepsy in a patient with MTOR mosaic mutation

2020

Abstract The MTOR gene encodes the mechanistic target of rapamycin (mTOR), which is a core component of the PI3K-AKT-mTOR signaling pathway. Postzygotic MTOR variants result in various mosaic phenotypes, referred to in OMIM as Smith-Kinsgmore syndrome or focal cortical dysplasia. We report here the case of a patient, with an MTOR mosaic gain-of-function variant (p.Glu2419Lys) in the DNA of 41% skin cells, who received compassionate off-label treatment with everolimus for refractory epilepsy. This 12-year-old-girl presented with psychomotor regression, intractable seizures, hypopigmentation along Blaschko's lines (hypomelanosis of Ito), asymmetric regional body overgrowth, and ocular anomali…

Efficacy and safety of Everolimus and Exemestane in hormone-receptor positive (HR+) human-epidermal-growth-factor negative (HER2−) advanced breast ca…

2017

Abstract Background The BOLERO-2 trial reported efficacy and safety of Everolimus (EVE) and Exemestane (EXE) combination in HR+ advanced breast cancer (ABC) patients. The BALLET trial further evaluated the safety of EVE-EXE in HR+ ABC patients, without reporting efficacy data. Aim of the EVA real-life study was to collect data of efficacy and safety of EVE-EXE combination in the clinical setting, as well as exploring efficacy according to EVE Dose-Intensity (DI) and to previous treatment with Fulvestrant. Patients and methods This study aimed to describe the outcome of ABC pts treated with EVE-EXE combination in terms of median duration of EVE treatment and ORR in a real-life setting. Resul…

Everolimus as first line therapy for pancreatic neuroendocrine tumours: current knowledge and future perspectives

2017

urpose Everolimus has been shown to be effective for advanced pancreatic neuroendocrine tumours (pNETs), but its positioning in the therapeutic algorithm for pNETs is matter of debate. Methods With the aim to shed light on this point, we performed an up-to-date critical review taking into account the results of both retrospective and prospective published studies, and the recommendations of international guidelines. In addition, we performed an extensive search on the Clinical Trial Registries databases worldwide, to gather information on the ongoing clinical trials related to this specific topic. Results We identified eight retrospective published studies, two prospective published studies…

Everolimus after hepatic arterial embolisation therapy of metastases from gastrointestinal neuroendocrine tumours: The FFCD 1104-EVACEL-GTE phase II …

2019

Abstract Background Hepatic arterial embolisation therapy (HAET) is a treatment of liver metastases of gastrointestinal neuroendocrine tumours (GI-NETs). HAET increases circulating vascular endothelial growth factor levels. Everolimus is a treatment in NETs that may have antiangiogenic activity. Methods This phase II study was conducted in patients with predominant and progressive liver metastases from GI-NETs. Everolimus was initiated 7–30 days after HAET. The hypothesis was that everolimus after HAET would increase hepatic progression-free survival (hPFS) rate at 24 months from 35% to 50%. Results Among the 74 patients included, 88% had small-bowel primary tumour, 43% had grade I and 57% …

Early outcome after implantation of Absorb bioresorbable drug-eluting scaffolds in patients with acute coronary syndromes

2013

The safety of BVS implantation in patients with a high risk for early thrombotic complications has not been studied. We report on the outcomes of patients with acute coronary syndromes (ACS) treated with bioresorbable, everolimus-eluting, vascular scaffolds (BVS).150 consecutive patients with ACS (194 lesions) treated with BVS between May 2012 and July 2013 were compared with a control group composed of 103 consecutive patients (129 lesions) who underwent everolimus drug-eluting stent (DES) implantation in the same time period. The incidence of major adverse cardiac events (MACE: death, non-fatal myocardial infarction, or reintervention) before discharge, at one month and six months was eva…