BE-POSITIVE: Beyond progression after tyrosine kinase inhibitor in EGFR- positive non small cell lung cancer patients: Results from a multicenter Italian observational study.

Objectives: Non-small-cell-lung-cancer (NSCLC) patients harbouring epidermal growth factor receptor (EGFR) mutations develop drug resistance after 9-12 months of EGFR tyrosine kinase inhibitors (TKIs) therapy pointing out the issue of the second-line treatment choice.

Materials And Methods: From June 2009 until May 2013 patients affected by advanced NSCLC harbouring EGFR mutations receiving first-line TKI were collected mainly retrospectively in 24 Italian Centers. Primary objective was to describe the percentage of EGFR mutated patients receiving second-line therapy after progression to first-line EGFR-TKIs assessing the type, the activity in terms of objective response rate (ORR), efficacy in terms of progression free survival (PFS) and overall survival (OS), and safety of second-line treatment.

Overcoming Resistance to EGFR Inhibitors in NSCLC.

Background: The clarification of several molecular pathways underlying the tumorigenesis has led to the development of several targeted drugs that have substantially improved the treatment of Non-Small-Cell Lung Cancer (NSCLC). The Epidermal Growth Factor Receptor (EGFR) is the target of several Tyrosine-Kinase Inhibitors (TKIs), some of them approved for treatment and others currently in clinical development. EGFR-TKIs markedly improve progression-free survival of patients with advanced NSCLC with EGFR mutations compared with chemotherapy.

Platinum-based chemotherapy in advanced non-small-cell lung cancer: optimal number of treatment cycles.

Platinum-based chemotherapy remains the standard-of-care for most patients affected by advanced non-small cell lung cancer (NSCLC). The platinum compounds currently used in NSCLC are cisplatin and carboplatin. The availability of new generation drugs has led to the adoption of schedules with lower doses of platinum compounds leading to increased tolerability.

Safety profiles of first-line therapies for metastatic non-squamous non-small-cell lung cancer.

Introduction: Lung cancer still represents the leading cause of death for cancer. About the 70% of diagnosis are in advanced-stage. Non-small-cell lung cancer (NSCLC) represents the 85% of all diagnosed lung cancers and non-squamous histology represents the 40% of all NSCLC.

Early precut sphincterotomy for difficult biliary access to reduce post-ERCP pancreatitis: a randomized trial.

Background And Study Aim: Precut sphincterotomy is a technique usually employed for difficult biliary cannulation during endoscopic retrograde cholangiopancreatography (ERCP) for the treatment of bile duct disease. It is a validated risk factor for post-ERCP pancreatitis (PEP), but it is not clear whether the risk is related to the technique itself or to the repeated biliary cannulation attempts preceding it. The primary aim of the study was to assess the incidence of PEP in early precut compared with the standard technique in patients with difficult biliary cannulation.

Anti-EGFR and antiangiogenic monoclonal antibodies in metastatic non-small-cell lung cancer.

Introduction: In recent years, several clinical trials have evaluated the efficacy and safety of biological therapies in lung cancer. Epidermal growth factor receptor (EGFR) and the axis vascular endothelial growth factor receptor (VEGF/VEGFR) are targeted by small molecules and monoclonal antibodies (mAbs), especially in non-squamous non-small-cell lung cancer (NSCLC).

Areas Covered: The current state of the art of anti-EGFR and antiangiogenic monoclonal antibodies in metastatic NSCLC is reviewed and discussed.

The Evolving Role of Nivolumab in Non-Small-Cell Lung Cancer for Second-Line Treatment: A New Cornerstone for Our Treatment Algorithms. Results From an International Experts Panel Meeting of the Italian Association of Thoracic Oncology.

Lung cancer is the leading cause of death from cancer worldwide that currently has only a few available treatment options in patients with no driver mutations. The therapeutic options for patients with non-small-cell lung cancer (NSCLC) who progress after first-line chemotherapy have been limited from a long time. Docetaxel has remained a cornerstone of second-line treatment for more than 20 years, but it is associated with an unfavorable safety profile.

Optimal drugs for second-line treatment of patients with small-cell lung cancer.

Introduction: Despite the high response rate to chemotherapy, there have been few advances in the treatment of small-cell lung cancer (SCLC) in the last decades. The state-of-the-art second-line therapy and future research developments in relapsed SCLC are reviewed.

Areas Covered: There are no optimal drugs for second-line treatment of recurrent SCLC but only agents registered for this use.

Red wine activates plasma membrane redox system in human erythrocytes.

In the present study, we report that polyphenols present in red wine obtained by a controlled microvinification process are able to protect human erythrocytes from oxidative stress and to activate Plasma Membrane Redox System (PMRS). Human plasma obtained from healthy subjects was incubated in the presence of whole red wine at a concentration corresponding to 9.13-73 μg/ml gallic acid equivalents to verify the capacity to protect against hypochlorous acid (HOCl)-induced plasma oxidation and to minimize chloramine formation.

Novel cytotoxic drugs in advanced nonsmall cell lung cancer.

Purpose Of Review: This article focuses on novel cytotoxic drugs for the treatment of patients with advanced nonsmall cell lung cancer (NSCLC) and describes their impact on disease outcome.

Recent Findings: Nab-paclitaxel and carboplatin as first-line treatment should be considered a therapeutic option, particularly in patients with squamous histology. Nedaplatin and docetaxel improves survival in Asiatic patients with squamous histology as compared with cisplatin and docetaxel.

Endocrinopathies induced by immune-checkpoint inhibitors in advanced non-small cell lung cancer.

The advent of immunotherapy has recently expanded the therapeutic options in advanced non-small cell lung cancer (NSCLC). In these patients, the recent efficacy demonstration of antibodies against immune checkpoints: the anti-programmed death-1 (PD-1) and anti-programmed death ligand-1 (PD-L1), has led to approval of nivolumab and pembrolizumab (anti-PD-1) in the treatment of advanced NSCLC. The mechanism of action of checkpoint inhibitors explains the development of autoimmune diseases as a side-effect of these medications.

Pharmacotherapeutic options for treating adverse effects of Cisplatin chemotherapy.

Introduction: Cisplatin is widely used in the treatment of several tumors such as lung, ovarian and testicular cancer with different degrees of effectiveness, and its use is burdened by some side effects.

Areas Covered: This review includes the most important cisplatin side effects such as neurotoxicity, nephrotoxicity, ototoxicity, nausea and vomiting. They can affect patient's quality of life and lead to treatment interruptions with effectiveness reduction.

Agents in the preclinical development stage for non-small cell lung cancer.

Despite recent advancements in identifying distinct molecular subtypes with driver oncogenes and advances in developing targeted treatments such as epidermal growth factor receptor and anaplastic lymphoma kinase inhibitors, current therapeutic approaches for tumors with no driver mutation have achieved a plateau of effectiveness. Thus, the overall outlook of lung cancer survival for most patients remains dismal. Moreover, the inevitable acquisition of resistance to targeted therapies has prompted significant efforts to develop second-generation inhibitors.

Current challenges of lung cancer care in an aging population.

Lung cancer is the most common cancer in the elderly with a high mortality rate. Despite the high incidence, the elderly are under-represented in clinical trials and under-treated in clinical practice. These patients have a higher prevalence of comorbid disease, higher polypharmacy interactions, and an increased risk of mortality and toxicity with cancer treatments, compared to younger patients.

Left Ventricular Wall Stress-Mass-Heart Rate Product and Cardiovascular Events in Treated Hypertensive Patients: LIFE Study.

In the Losartan Intervention for End Point Reduction in Hypertension (LIFE) study, 4.8 years' losartan- versus atenolol-based antihypertensive treatment reduced left ventricular hypertrophy and cardiovascular end points, including cardiovascular death and stroke. However, there was no difference in myocardial infarction (MI), possibly related to greater reduction in myocardial oxygen demand by atenolol-based treatment.

Anti PD-1 and PDL-1 Immunotherapy in the Treatment of Advanced Non- Small Cell Lung Cancer (NSCLC): A Review on Toxicity Profile and its Management.

The better understanding of immunology and antitumor immune responses have prompted the development of novel immunotherapy agents like PD-1 checkpoint inhibitors (anti-PD-1 and anti- PDL-1 antibodies) that improve the capacity of the immune system to acknowledge and delete tumors, including lung cancer. Currently, two anti-PD-1 (nivolumab and pembrolizumab) and one anti- PD-L1 (MPDL-3280A) agents are in advanced stages of development in advanced or metastatic non-small cell lung cancer (NSCLC). Among these, nivolumab demonstrated a survival benefit versus docetaxel in refractory squamous NSCLC, reporting 41% reduction in risk of death (median overall survival: 9.

Overcoming resistance to targeted therapies in NSCLC: current approaches and clinical application.

The discovery that a number of aberrant tumorigenic processes and signal transduction pathways are mediated by druggable protein kinases has led to a revolutionary change in nonsmall cell lung cancer (NSCLC) treatment. Epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) are the targets of several tyrosine kinase inhibitors (TKIs), some of them approved for treatment and others currently in clinical development. First-generation agents offer, in target populations, a substantial improvement of outcomes compared with standard chemotherapy in the treatment of advanced NSCLC.

New Antiangiogenetic Therapy Beyond Bevacizumab in the Treatment of Advanced Non Small Cell Lung Cancer.

Lung cancer is the leading cause of death from cancer worldwide with limited available treatment options in absence of specific molecular alteration. New therapeutic approaches for addressing non small cell lung cancer (NSCLC) are urgently needed. Angiogenesis plays a central role in the tumor growth and metastatic dissemination which stimulates multiple cells to build new abnormal microvessels and leads to tumor microenvironment alterations.

Oral chemotherapy and patient perspective in solid tumors: a national survey by the Italian association of medical oncology.

Aim: To assess patient perception toward oral chemotherapy for solid tumors, the Italian Association of Medical Oncology performed a large multi-institutional national survey.

Methods: A 17-item anonymous questionnaire including 7 general and 10 investigational questions with free-text, single-choice, or multiple-choice answers was administered. Analysis of response distribution according to predefined factors was described by summary measures and conducted by χ2 test and other nonparametric tests.

Safety and Efficacy of Buparlisib (BKM120) in Patients with PI3K Pathway-Activated Non-Small Cell Lung Cancer: Results from the Phase II BASALT-1 Study.

Introduction: The phosphatidylinositol 3-kinase (PI3K) pathway promotes tumor growth and treatment resistance in non-small cell lung cancer (NSCLC). The aim of the open-label, two-stage, Phase II study BASALT-1 (NCT01820325) was to investigate the pan-PI3K inhibitor buparlisib (BKM120) in patients with PI3K pathway-activated, relapsed NSCLC.

Methods: After prescreening for PI3K pathway activation, patients with PI3K pathway-activated, metastatic, squamous or nonsquamous NSCLC, who had relapsed after prior systemic antineoplastic therapy, were enrolled.

Imaging of body packing: errors and medico-legal issues.

Body packing is the ingestion or insertion in the human body of packed illicit substances. Over the last 20 years, drug smuggling has increased global and new means of transport of narcotics have emerged. Among these, the most frequent one is the gastrointestinal tract: from mouth to anus, vagina, and ears.

EGFR mutations in lung cancer: from tissue testing to liquid biopsy.

ABSTRACT  The presence of EGFR mutations predicts the sensitivity to EGF receptor (EGFR)-tyrosine kinase inhibitors in a molecularly defined subset of non-small-cell lung carcinoma (NSCLC) patients. For this reason, EGFR testing of NSCLC is required to provide personalized treatment options and better outcomes for NSCLC patients. As surgery specimens are not available in the majority of NSCLC, other currently available DNA sources are small biopsies and cytological samples, providing however limited and low-quality material.

Extensive in vitro gastrointestinal digestion markedly reduces the immune-toxicity of Triticum monococcum wheat: implication for celiac disease.

Scope: The ancient diploid Triticum monococcum is of special interest as a candidate low-toxic wheat species for celiac disease patients. Here, we investigated how an in vitro gastro-intestinal digestion, affected the immune toxic properties of gliadin from diploid compared to hexaploid wheat.

Methods And Results: Gliadins from Triticum monococcum, and Triticum aestivum cultivars were digested using either a partial proteolysis with pepsin-chymotrypsin, or an extensive degradation that used gastrointestinal enzymes including the brush border membrane enzymes.

Cilengitide combined with cetuximab and platinum-based chemotherapy as first-line treatment in advanced non-small-cell lung cancer (NSCLC) patients: results of an open-label, randomized, controlled phase II study (CERTO).

Background: This multicentre, open-label, randomized, controlled phase II study evaluated cilengitide in combination with cetuximab and platinum-based chemotherapy, compared with cetuximab and chemotherapy alone, as first-line treatment of patients with advanced non-small-cell lung cancer (NSCLC).

Patients And Methods: Patients were randomized 1:1:1 to receive cetuximab plus platinum-based chemotherapy alone (control), or combined with cilengitide 2000 mg 1×/week i.v.

The Role of Ivabradine in Cardiac Rehabilitation in Patients With Recent Coronary Artery Bypass Graft.

Background: Little is known about ivabradine in cardiac rehabilitation in patients with coronary artery bypass graft (CABG).

Methods: In this prospective, randomized study, suitable patients admitted for cardiac rehabilitation after recent CABG were randomized to ivabradine 5 mg twice a day + standard medical therapy including bisoprolol 1.25 mg once daily (group I-BB, n = 38) or standard medical therapy including bisoprolol 2.