Search results for "First line"

Fundamentals on the Molecular Mechanism of Action of Antimicrobial Peptides

2019

Abstract Antimicrobial peptides (AMPs) are produced by several organisms as their first line of defense. Constituted by amino acids, they may present different mechanisms of action. The antimicrobial activity can be used by the peptide-producing organism itself, as innate immune strategy, or in the industry, applying as natural source preservatives. Understanding the possibilities of the operation of these compounds is a prerequisite for the development of effective uses, as well as for the establishment of combinations, which can even expand their applications considering the possibilities of genetic manipulations. Thus, the objective of this article is to review the basic principles of AM…

Diagnostic odyssey in severe neurodevelopmental disorders: toward clinical whole-exome sequencing as a first-line diagnostic test

2016

The current standard of care for diagnosis of severe intellectual disability (ID) and epileptic encephalopathy (EE) results in a diagnostic yield of ∼50%. Affected individuals nonetheless undergo multiple clinical evaluations and low-yield laboratory tests often referred to as a 'diagnostic odyssey'. This study was aimed at assessing the utility of clinical whole-exome sequencing (WES) in individuals with undiagnosed and severe forms of ID and EE, and the feasibility of its implementation in routine practice by a small regional genetic center. We performed WES in a cohort of 43 unrelated individuals with undiagnosed ID and/or EE. All individuals had undergone multiple clinical evaluations a…

A randomized, open-label, two-arm phase II trial comparing the efficacy of sequential ipilimumab (ipi) versus best supportive care (BSC) following fi…

2016

4011Background: Pts with advanced gastric cancer have a poor prognosis with median overall survival (OS) of ~1 yr. Ipi is a monoclonal antibody that enhances T-cell activation and T-effector cell t...

Maintenance therapy with avelumab (MSB0010718C; anti-PD-L1) vs continuation of first-line chemotherapy in patients with unresectable, locally advance…

2016

TPS4134Background: Programmed death-1 receptor ligand (PD-L1) is a key therapeutic target in the reactivation of the immune response against multiple cancers. Avelumab* is a fully human anti-PD-L1 ...

Phase 1b/3 study of avelumab-based combination regimens in patients with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL).

2017

TPS7575 Background: Approximately 50% of patients (pts) with advanced DLBCL are refractory to or relapse following first line R-CHOP therapy. Pts with R/R DLBCL have limited treatment options and a poor prognosis. This study assesses immunotherapy-based regimens containing avelumab (a fully human IgG1 anti–PD-L1 antibody) in combination with utomilumab (a novel 4-1BB agonist), azacitidine, rituximab, and/or conventional chemotherapy (CT; bendamustine) in pts with R/R DLBCL. Methods: JAVELIN DLBCL (NCT02951156) is a global, multicenter, randomized, open-label, 2-component(phase 1b followed by phase 3) study of avelumab-based combination regimens in R/R DLBCL. In phase 1b, up to 84 pts will …

Checkpoint inhibitors for gastroesophageal cancers: dissecting heterogeneity to better understand their role in first-line and adjuvant therapy

2020

Gastroesophageal adenocarcinoma (GEA) and squamous esophageal cancer (ESCC) are responsible for1 million deaths annually globally. Until now, patients with metastatic GEA and ESCC could anticipate survival of1 year. Anti- programmed cell death protein 1 (anti-PD-1) monotherapy has demonstrated modest efficacy in previously treated GEA and ESCC. In 2020, four pivotal trials have established anti-PD-1 therapy as a new standard of care for selected GEA and ESCC patients as first-line advanced and adjuvant therapy. In this review, we discuss the recent results of the CheckMate 649, ATTRACTION-4, KEYNOTE-590 and CheckMate 577 trials. We consider these results in the context of current standards …

Aflibercept in combination with irinotecan, fluorouracil and leucovorin (FOLFIRI) as first-line chemotherapy in metastatic colorectal cancer (mCRC) p…

2018

The best strategy for RAS wild-type metastatic colorectal cancer patients in first-line treatment: A classic and Bayesian meta-analysis

2018

Background: At present, there is uncertainty on the best systemic treatment in first-line setting for RAS wild-type (WT) metastatic colorectal cancer (mCRC) patients. Indeed, several chemotherapy and biologics combinations showed an improvement on survival. We performed a systematic review with a pair-wise and bayesan meta-analysis to rank the best strategy for these patients. Methods: A systematic literature search through March 2017 was performed to evaluate the association between several treatment combinations and overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and toxicity rate (TR) in RAS WT mCRC patients. Data were extracted from studies and pooled…

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…

Development of artemisinin resistance in malaria therapy

2019

Malaria affects 200 million people worldwide. Today, the most successful treatments are artemisinin-based combination therapies (ACT). Resistance has already been described for the elder anti-malarials chloroquine, sulfadoxine-pyrimethamine and mefloquine. Unfortunately, over the last few years there has also been an emerging resistance to the successfully used drug artemisinin, especially in African and Asian countries. A systematic PubMed literature research was conducted for studies published between January 2002 and December 2018. Despite ACTs continue to be first line treatment, the number of studies is rising reporting on artemisinin resistance mutations. Most publications reported on…