A phase II double-blind study to investigate efficacy and safety of two doses of the triple angiokinase inhibitor BIBF 1120 in patients with relapsed advanced non-small-cell lung cancer.

Background: To assess the efficacy, safety, tolerability and pharmacokinetics of BIBF 1120 in patients with stage IIIB/IV non-small-cell lung cancer (NSCLC).

Methods: Patients with locally advanced or metastatic relapsed NSCLC in whom first- or second-line platinum-based chemotherapy failed were randomly allocated to daily 250 mg BIBF 1120 b.i.

Mutations in the epidermal growth factor receptor gene in non-small cell lung cancer: Impact on treatment beyond gefitinib and erlotinib.

Epidermal growth factor receptor (EGFR)-activating mutations in non-small cell lung cancer (NSCLC) are molecular targets for treatment with gefitinib and erlotinib, often resulting in improved response and prolonged progression-free survival. Resistance to these drugs, which develops during treatment, is a problem of paramount importance. Several mechanisms of "acquired resistance" have been discovered and treatments for this specific entity are on the horizon.

First-cycle rash and survival in patients with advanced non-small-cell lung cancer receiving cetuximab in combination with first-line chemotherapy: a subgroup analysis of data from the FLEX phase 3 study.

Background: The randomised phase 3 First-Line Erbitux in Lung Cancer (FLEX) study showed that the addition of cetuximab to cisplatin and vinorelbine significantly improved overall survival compared with chemotherapy alone in the first-line treatment of advanced non-small-cell lung cancer (NSCLC). The main cetuximab-related side-effect was acne-like rash. Here, we assessed the association of this acne-like rash with clinical benefit.

Reviewing the safety of erlotinib in non-small cell lung cancer.

Importance Of The Field: Erlotinib, a potent inhibitor of EGFR activity, is approved as a monotherapy for the treatment of advanced NSCLC and in combination with gemcitabine for advanced pancreatic cancer. The oral administration and manageable toxicity of erlotinib, along with its similar efficacy to chemotherapy, make it an important option as either maintenance therapy or in second-/third-line for patients with NSCLC who have previously received first-line chemotherapy. It is also an emerging option in other treatment settings in NSCLC.

Indacaterol once-daily is equally effective dosed in the evening or morning in COPD.

Unlabelled: Indacaterol is a novel, inhaled, long-acting β(2)-agonist providing 24-h bronchodilation with once-daily (o.d.) dosing in patients with COPD.

Examining the safety profile of angiogenesis inhibitors: implications for clinical practice.

Dysregulation of angiogenesis in solid tumors enables tumor growth and metastasis. Receptors that mediate angiogenesis, and their ligands, have been identified; among these, vascular endothelial growth factor (VEGF) and its receptor tyrosine kinase play a central role. In non-small cell lung cancer (NSCLC), clinical benefit has been shown with bevacizumab, which blocks VEGF binding to its receptors.

Erlotinib in advanced non-small cell lung cancer: efficacy and safety findings of the global phase IV Tarceva Lung Cancer Survival Treatment study.

Introduction: Erlotinib is a small molecule inhibitor of epidermal growth factor receptor tyrosine-kinase activity that has been shown to significantly increase survival for patients with previously treated advanced non-small cell lung cancer. Here, we report safety and efficacy data from a large, global, open-label, phase IV trial of erlotinib (Tarceva Lung Cancer Survival Treatment).

Methods: Patients who had previously failed on chemotherapy or radiotherapy and were unsuitable for these treatments were treated with oral erlotinib (150 mg/d) until disease progression or unacceptable toxicity.

A major step towards individualized therapy of lung cancer with gefitinib: the IPASS trial and beyond.

Most patients with non-small-cell lung cancer (NSCLC) present with advanced disease and have poor long-term prognosis. Gefitinib, a targeted therapy that prevents ATP binding in the tyrosine kinase domain of the EGF receptor, has been subject to comprehensive clinical development. A Phase III trial has demonstrated that gefitinib is superior to carboplatin/paclitaxel in terms of progression-free survival and objective response rate, as first-line treatment for pulmonary adenocarcinoma among never-smokers or former light smokers in East Asia (the IRESSA Pan-Asia Study), with the presence of an EGFR mutation being a strong predictor of the effect of gefitinib compared with carboplatin/paclitaxel.

BIBF 1120 for the treatment of non-small cell lung cancer.

Importance Of The Field: For patients with advanced non-small cell lung cancer (NSCLC), chemotherapy offers modest benefits and outcomes are poor. Angiogenesis, the formation of new blood vessels from the pre-existing vasculature, is a fundamental process for tumor growth and development. Tumor vasculature is therefore emerging as an important target for cancer therapy.

Decreasing cardiac chamber sizes and associated heart dysfunction in COPD: role of hyperinflation.

Background: Little is known about the role of abnormal lung function in heart size and heart dysfunction in patients with COPD. We studied the relationship of lung function with heart size and heart dysfunction and associated consequences for 6-min walk distance (6MWD) in patients with COPD of different severitites.

Methods: In 138 patients with COPD (Global Initiative for Obstructive Lung Disease [GOLD] I-IV), we measured the size of all cardiac chambers, left ventricular diastolic dysfunction (relaxation and filling), and global right ventricular dysfunction (Tei-index) by echocardiography.

Sunitinib in combination with gemcitabine plus cisplatin for advanced non-small cell lung cancer: a phase I dose-escalation study.

Purpose: To determine the maximum tolerated dose (MTD) of sunitinib plus gemcitabine/cisplatin for first-line treatment of patients with advanced non-small cell lung cancer (NSCLC). Safety, pharmacokinetics, and antitumor activities were evaluated.

Methods: Patients ≥18 years with Eastern Cooperative Oncology Group performance status 0/1 and stage IIIB/IV NSCLC were included in this open-label, multicenter, dose-escalation phase I study.

A multicentre phase II gene expression profiling study of putative relationships between tumour biomarkers and clinical response with erlotinib in non-small-cell lung cancer.

Background: Identification of appropriate markers for predicting clinical benefit with erlotinib in non-small-cell lung cancer (NSCLC) may be able to guide patient selection for treatment. This open-label, multicentre, phase II trial aimed to identify genes with potential use as biomarkers for clinical benefit from erlotinib therapy.

Methods: Adults with stage IIIb/IV NSCLC in whom one or more chemotherapy regimen had failed were treated with erlotinib (150 mg/day).

Systemic inflammation in chronic obstructive pulmonary disease and asthma: relation with comorbidities.

Markers of systemic inflammation have been shown to be elevated in blood of patients with chronic obstructive pulmonary disease (COPD) when compared with control subjects without COPD. The origin of systemic inflammation in COPD is unclear. COPD is often accompanied by other chronic diseases that are also associated with systemic inflammation, such as chronic heart failure, diabetes, and arteriosclerosis.

Pemetrexed in the treatment of malignant mesothelioma: results from an expanded access program in Germany.

An international expanded access program was initiated to provide access to treatment with pemetrexed prior registration and reimbursement for malignant mesothelioma (MM). Chemonaïve and pretreated patients with inoperable MM of the pleura or peritoneum were eligible. This report describes the results obtained in German centers.

Peak inspiratory flow through the Genuair inhaler in patients with moderate or severe COPD.

The Genuair inhaler is a new multidose dry powder inhaler for the delivery of aclidinium bromide - a novel, long-acting, muscarinic antagonist in development for the treatment of chronic obstructive pulmonary disease (COPD). The primary aim of this study was to assess the inspiratory flow characteristics through Genuair in patients with moderate or severe COPD. Using a three-period cross-over design, 48 patients were randomised to inhale placebo powder through Genuair, HandiHaler A (slow, deep inhalation as per manufacturer's instructions) or HandiHaler B (fast, forceful inhalation).

SCH527123, a novel CXCR2 antagonist, inhibits ozone-induced neutrophilia in healthy subjects.

SCH527123 is a novel, selective CXC chemokine receptor 2 antagonist that inhibits neutrophil activation and modulates neutrophil trafficking in animal models, characteristics that may be beneficial in the treatment of conditions with unbalanced pulmonary neutrophilia, such as chronic obstructive pulmonary disease. The purpose of this proof-of-principle study was to determine whether SCH527123 inhibits ozone-induced neutrophil recruitment in healthy humans. In a randomised, double-blind, placebo-controlled, three-way crossover study, oral SCH527123 (50 mg once daily, 4 days), prednisolone (50 mg once), or placebo was alternated with 2-week washouts.

The metabolic syndrome in patients with chronic bronchitis and COPD: frequency and associated consequences for systemic inflammation and physical inactivity.

Background: The metabolic syndrome is a condition frequently found among individuals > 60 years of age. It predisposes affected individuals to systemic inflammation and physical inactivity. Systemic inflammation and physical inactivity are relevant extrapulmonary markers of morbidity and mortality in patients with COPD.

Gefitinib in the treatment of advanced non-small-cell lung cancer.

Most patients with non-small-cell lung cancer (NSCLC) present with advanced disease and their long-term prognosis remains poor, even after platinum-based chemotherapy. EGF receptor (EGFR)-targeted therapies, such as gefitinib, have been subject to comprehensive clinical development. Several Phase II and III trials have evaluated the clinical efficacy of gefitinib as monotherapy in pretreated patients with advanced NSCLC, as well as both monotherapy and combined with chemotherapy in chemo-naive patients.

Phase III trial of cisplatin plus gemcitabine with either placebo or bevacizumab as first-line therapy for nonsquamous non-small-cell lung cancer: AVAil.

Purpose: Bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor, improves survival when combined with carboplatin/paclitaxel for advanced nonsquamous non-small-cell lung cancer (NSCLC). This randomized phase III trial investigated the efficacy and safety of cisplatin/gemcitabine (CG) plus bevacizumab in this setting.

Patients And Methods: Patients were randomly assigned to receive cisplatin 80 mg/m2 and gemcitabine 1,250 mg/m(2) for up to six cycles plus low-dose bevacizumab (7.

Efficacy and safety of indacaterol, a new 24-hour beta2-agonist, in patients with asthma: a dose-ranging study.

Background: Indacaterol is a new once-daily inhaled beta(2)-agonist in clinical development for asthma as a component of a fixed-dose combination with an inhaled corticosteroid.

Objectives: To investigate the efficacy and safety of indacaterol in patients with chronic persistent asthma.

Methods: A total of 115 patients were randomized in a double-blind, incomplete-block cross-over design to sequences of four 7-day treatment periods (separated by 7-day washouts) with indacaterol 100, 200, 300, 400, or 600 micro g or placebo, once daily, via single-dose dry-powder inhaler.

Physical activity in patients with COPD.

The present study aimed to measure physical activity in patients with chronic obstructive pulmonary disease (COPD) to: 1) identify the disease stage at which physical activity becomes limited; 2) investigate the relationship of clinical characteristics with physical activity; 3) evaluate the predictive power of clinical characteristics identifying very inactive patients; and 4) analyse the reliability of physical activity measurements. In total, 163 patients with COPD (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I-IV; BODE (body mass index, airway obstruction, dyspnoea, exercise capacity) index score 0-10) and 29 patients with chronic bronchitis (normal spirometry; former GOLD stage 0) wore activity monitors that recorded steps per day, minutes of at least moderate activity, and physical activity levels for 5 days (3 weekdays plus Saturday and Sunday). Compared with patients with chronic bronchitis, steps per day, minutes of at least moderate activity and physical activity levels were reduced from GOLD stage II/BODE score 1, GOLD stage III/BODE score 3/4 and from GOLD stage III/BODE score 1, respectively.

Advances in anti-VEGF and anti-EGFR therapy for advanced non-small cell lung cancer.

Chemotherapy has reached a therapeutic plateau in the treatment of advanced non-small cell lung cancer (NSCLC), and effective, better-tolerated treatment strategies are needed. An improved understanding of the molecular processes underlying tumor biology has led to the development of therapies that target these processes. Intracellular signaling pathways related to the vascular endothelial growth factor and the epidermal growth factor receptor both play a central role in tumorigenesis as well as tumor growth, and are therefore rational targets for anti-cancer drug development.

Assessing airway inflammation in clinical practice - experience with spontaneous sputum analysis.

Background: The assessment of airway inflammation for the diagnosis of asthma or COPD is still uncommon in pneumology-specialized general practices. In this respect, the measurement of exhaled nitric oxide (NO), as a fast and simple methodology, is increasingly used. The indirect assessment of airway inflammation, however, does have its limits and therefore there will always be a need for methods enabling a direct evaluation of airway inflammatory cell composition.

In contrast to lung fibroblasts--no signs of senescence in skin fibroblasts of patients with emphysema.

Smoking is known to be linked to skin ageing and there is evidence for premature senescence of parenchymal lung fibroblasts in emphysema. To reveal whether the emphysema-related changes in cellular phenotype extend beyond the lung, we compared the proliferation characteristics of lung and skin fibroblasts between patients with and without emphysema. Parenchymal lung fibroblasts and skin fibroblasts from the upper torso (thus limiting sun exposure bias) were obtained from patients without, or with mild, or with moderate to severe emphysema undergoing lung surgery.

Effect of the oral leukotriene B4 receptor antagonist LTB019 on inflammatory sputum markers in patients with chronic obstructive pulmonary disease.

This study aimed to evaluate the effect of a LTB4 receptor antagonist on inflammatory markers in induced sputum, in particular sputum neutrophilia, in ex-smokers with moderate stable chronic obstructive pulmonary disease (COPD). The trial followed a double-blind, randomized, cross-over design including two treatment periods (4 weeks) separated by a 4-week washout period. Sputum inductions and lung function measurements were carried out at the beginning of each period, and after 2 and 4 weeks.