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Bad Berka, Germany

Laskin J.,BC Cancer Agency | Crino L.,Hospital S Maria della Misericordia | Felip E.,University of Barcelona | Franke F.,Hospital de Caridade | And 5 more authors.
Journal of Thoracic Oncology | Year: 2012

Introduction: Safety of Avastin in Lung (MO19390) was an international, open-label, single-arm study, which assessed the safety and efficacy of first-line bevacizumab (Avastin®) in combination with standard chemotherapy in patients (n = 2212) with advanced or recurrent non-small cell lung cancer (NSCLC). A preplanned subgroup analysis was performed to examine these outcomes in elderly patients older than 65 years. Methods: Eligible patients with nonsquamous NSCLC received up to six cycles of bevacizumab (7.5 or 15 mg/kg) plus any standard of care chemotherapy. Patients who did not experience disease progression after induction therapy continued bevacizumab therapy until disease progression or unacceptable toxicity. The primary end point was safety; secondary end points included time to disease progression (TTP) and overall survival (OS). Results: Data were evaluated for 623 patients older than 65 years (mean age 70.6). The majority were Whites (86.2%) with stage IV disease (79.7%) and had adenocarcinoma (83.5%). The incidence of adverse events (AEs) of special interest was similar for elderly and younger patients (any grade bleeding 38.2% versus 38.3%; any grade hypertension 33.1% versus 30.6%; any grade proteinuria 33.4% versus 29.3%). Most AEs were grade less than or equal to 2. Serious AEs were reported in 45.3 and 34.7% of elderly and younger patients, respectively. Median OS was similar in elderly and younger patients (14.6 months in both age groups), as were TTP (8.2 versus 7.6 months), response rate (49.3% versus 52.4%), and disease control rate (89.3% versus 88.4%). Similar results were seen in a post hoc comparison of the older than 70 years and 70 years or younger subgroups: TTP was 8.6 months versus 7.7 months, respectively; OS was 14.6 months in both subgroups; response rate was 49% and 52%, respectively; incidence of AEs of special interest was comparable. Conclusion: Patients older than 65 years with nonsquamous NSCLC derive a similar clinical benefit from first-line bevacizumab-based therapy as their younger counterparts and do not experience increased toxicity. © 2011 by the International Association for the Study of Lung Cancer.

Ramalingam S.S.,Emory University | Spigel D.R.,Sarah Cannon Research Institute and Tennessee Oncology | Chen D.,Roche Holding AG | Steins M.B.,University of Heidelberg | And 10 more authors.
Journal of Clinical Oncology | Year: 2011

Purpose: R1507 is a selective, fully human, recombinant monoclonal antibody (immunoglobulin G1 subclass) against insulin-like growth factor-1 receptor (IGF-1R). The strong preclinical evidence supporting coinhibition of IGF-1R and epidermal growth factor receptor (EGFR) as anticancer therapy prompted this study. Patients and Methods: Patients with advanced-stage non-small-cell lung cancer (NSCLC) with progression following one or two prior regimens, Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2, and measurable disease were eligible. Patients were randomly assigned to receive erlotinib (150 mg orally once a day) in combination with either placebo, R1507 9 mg/kg weekly, or R1507 16 mg/kg intravenously once every 3 weeks. Treatment cycles were repeated every 3 weeks. The primary end point was comparison of the 12-week progression-free survival (PFS) rate. Results: In all, 172 patients were enrolled: median age, 61 years; female, 33%; never-smokers, 12%; and performance status 0 or 1, 88%. The median number of R1507 doses was six for the weekly arm and 3.5 for the every-3-weeks arm. Grades 3 to 4 adverse events occurred in 37%, 44%, and 48% of patients with placebo, R1507 weekly, and R1507 every 3 weeks, respectively. The 12-week PFS rates were 39%, 37%, and 44%, and the median overall survival was 8.1, 8.1, and 12.1 months for the three groups, respectively, with statistically nonsignificant hazard ratios. The 12-week PFS rate in patients with KRAS mutation was 36% with R1507 compared with 0% with placebo. Conclusion: The combination of R1507 with erlotinib did not provide PFS or survival advantage over erlotinib alone in an unselected group of patients with advanced NSCLC. Predictive biomarkers are essential for further development of combined inhibition of IGF-1R and EGFR. © 2011 by American Society of Clinical Oncology.

Kohler L.H.,Friedrich - Schiller University of Jena | Mireskandari M.,Friedrich - Schiller University of Jena | Knosel T.,Friedrich - Schiller University of Jena | Knosel T.,Ludwig Maximilians University of Munich | And 6 more authors.
Virchows Archiv | Year: 2012

FGFR1 is a receptor tyrosine kinase of which the ligands belong to the fibroblast growth factor family. To evaluate the significance of FGFR1 in lung cancer, we analysed tumours by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Tissue microarrays were constructed containing 380 lung cancer samples including squamous cell carcinomas (SCC), adenocarcinomas (ADC), non-small cell lung cancer not otherwise specified, metastases, neuroendocrine tumours, large cell lung cancer and small cell lung cancer. FGFR1 expression was analysed by IHC and scored semi-quantitatively by a four-tier approach (0, 1, 2, 3). Using dual-colour interphase FISH with probes specific for the locus on 8p12 and the centromere of chromosome 8 (CEN8), copy numbers of FGFR1 were determined. High expression of FGFR1 was associated with increased FGFR1 gene copy numbers in squamous cell carcinoma (p∈<∈0.001). The FGFR1 locus was equally affected by copy number losses and gains. The higher FGFR1 gene copy numbers in SCC compared to ADC did not reach statistical significance. High copy number amplification of FGFR1 was a very rare event, the FGFR1/CEN8 signal ratio reaching a maximum value of 2.75. There were no significant associations between FGFR1 and clinicopathological parameters. Fibroblast growth factor signalling represents an interesting therapeutic target in lung cancer. However, the pathways are complex with potential oncogenic and anti-oncogenic activities. Our data may help to define criteria for selecting patients that may benefit from these new therapeutic options. © 2012 Springer-Verlag.

Girdauskas E.,Central Clinic Bad Berka | Rouman M.,Central Clinic Bad Berka | Disha K.,Central Clinic Bad Berka | Espinoza A.,Central Clinic Bad Berka | And 7 more authors.
European Journal of Cardio-thoracic Surgery | Year: 2016

OBJECTIVES: We prospectively examined functional characteristics of the aortic root and transvalvular haemodynamic flow in order to define factors associated with the severity of aortopathy in patients undergoing surgery for bicuspid aortic valve (BAV) stenosis. METHODS: A total of 103 consecutive patients with BAV stenosis (mean age 61 ± 9 years, 66% male) underwent aortic valve replacement ± concomitant aortic surgery from January 2012 through March 2014. All patients underwent preoperative cardiac magnetic resonance imaging (MRI) in order to evaluate the systolic transvalvular flow and the following functional parameters: (i) angulation between the left ventricular outflow axis and the aortic root, (ii) geometrical orientation of residual aortic valve orifice and (iii) BAV cusp fusion pattern. MRI data were used to guide sampling of the ascending aorta during surgery [i.e. jet-sample from the area where the flow-jet impacts on the aortic wall and control sample from the opposite aortic wall (obtained from the aortotomy site)]. Aortopathy was quantified by means of a histological sum-score (0 to 21+) in each sample. RESULTS: A significant correlation was found between histological sum-score in the jet-sample and the angle between the LV outflow axis and the aortic root (r = 0.6, P = 0.007). Moreover, there was a linear correlation between proximal aortic diameter and the angle between systolic flow-jet and ascending aortic wall (r = 0.5, P = 0.006). Logistic regression identified the angle between the LV outflow axis and the aortic root (OR 1.1, P = 0.04) and the angle between the flow-jet and the aortic wall (OR 1.2, P = 0.001) as independent predictors of an indexed proximal aortic diameter ≥ 22 mm/m2. CONCLUSIONS: Functional parameters of the aortic root may be used to predict the severity of aortopathy in patients with BAV stenosis, and may be useful in predicting future risk of aortic disease in such patients. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Girdauskas E.,Central Clinic Bad Berka | Rouman M.,Central Clinic Bad Berka | Disha K.,Central Clinic Bad Berka | Scholle T.,Central Clinic Bad Berka | And 5 more authors.
European Journal of Cardio-thoracic Surgery | Year: 2014

Objectives: The purpose of this study was to analyse the correlation between preoperative systolic transvalvular flow patterns and proximal aortic wall lesions in patients undergoing surgery for bicuspid aortic valve (BAV) stenosis. Methods: A total of 48 consecutive patients with BAV stenosis (mean age 58 ± 9 years, 65% male) underwent aortic valve replacement (AVR) ± proximal aortic surgery from January 2012 through February 2013. Preoperative cardiac phase-contrast cine magnetic resonance imaging (MRI) assessment was performed in all patients in order to detect the area of maximal flow-induced stress in the proximal aorta. Based on these MRI data, two aortic wall samples (i.e. area of the maximal stress (jet sample) and the opposite aortic wall (control sample)) were collected during AVR surgery. Aortic wall changes were graded based on a summation of seven histological criteria (each scored from 0 to 3). Histological sum score (0-21) was separately calculated and compared between the two aortic samples (i.e. jet sample vs control sample). Results: An eccentric transvalvular flow jet hitting the proximal aortic wall could be identified in all 48 (100%) patients. The mean histological sum score was significantly higher in the jet sample vs control sample areas of the aorta (i.e. 4.1 ± 1.8 vs 2.2 ± 1.5, respectively) (P = 0.02). None of the patients had a higher sum score value in the control sample. Conclusions: Our study demonstrates a strong correlation between the systolic pattern of the transvalvular flow jet and asymmetric proximal aortic wall changes in patients undergoing AVR for BAV stenosis. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

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