Hospital Grosshansdorf

Großhansdorf, Germany

Hospital Grosshansdorf

Großhansdorf, Germany

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Reck M.,Hospital Grosshansdorf | Bondarenko I.,Dnepropetrovsk City Hospital | Luft A.,Leningrad Regional Clinical Hospital | Serwatowski P.,Specjalistyczny Szpital im | And 5 more authors.
Annals of Oncology | Year: 2013

Ipilimumab, an anti-CTLA4 monoclonal antibody, demonstrated survival benefit in melanoma with immune-related (ir) adverse events (irAEs) managed by the protocol-defined guidelines. This phase 2 study evaluated ipilimumab + paclitaxel (Taxol)/carboplatin in extensive-disease-small-cell lung cancer (ED-SCLC). Design: Patients (n = 130) with chemotherapy-naïve ED-SCLC were randomized 1: 1: 1 to receive paclitaxel (175 mg/m2)/carboplatin (area under the curve = 6) with either placebo (control) or ipilimumab 10 mg/kg in two alternative regimens, concurrent ipilimumab (ipilimumab + paclitaxel/carboplatin followed by placebo + paclitaxel/carboplatin) or phased ipilimumab (placebo + paclitaxel/carboplatin followed by ipilimumab + paclitaxel/carboplatin). Treatment was administered every3 weeks for a maximum of 18 weeks (induction), followed by maintenance ipilimumab or placebo every 12 weeks. End points included progression-free survival (PFS), irPFS, best overall response rate (BORR); irBORR,overall survival (OS), and safety. Results: Phased ipilimumab, but not concurrent ipilimumab, improved irPFS versus control [HR (hazard ratio) = 0.64;P = 0.03]. No improvement in PFS (HR = 0.93; P = 0.37) or OS (HR = 0.75; P = 0.13) occurred. Phased ipilimumab,concurrent ipilimumab and control, respectively, were associated with median irPFS of 6.4, 5.7 and 5.3 months;median PFS of 5.2, 3.9 and 5.2 months; median OS of 12.9, 9.1 and 9.9 months. Overall rates of grade 3/4 irAEs were 17, 21 and 9% for phased ipilimumab, concurrent ipilimumab and control, respectively. Conclusion: These results suggest further investigation of ipilimumab in ED-SCLC. © The Author 2012. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.


Paz-Ares L.,University of Seville | de Marinis F.,San Camillo Forlanini Hospital | Dediu M.,Institute of Oncology Bucharest | Thomas M.,University of Heidelberg | And 13 more authors.
The Lancet Oncology | Year: 2012

Background: Patients with advanced non-squamous non-small-cell lung cancer (NSCLC) benefit from pemetrexed maintenance therapy after induction therapy with a platinum-containing, non-pemetrexed doublet. The PARAMOUNT trial investigated whether continuation maintenance with pemetrexed improved progression-free survival after induction therapy with pemetrexed plus cisplatin. Methods: In this double-blind, multicentre, phase 3, randomised placebo-controlled trial, patients with advanced non-squamous NSCLC aged 18 years or older, with no previous systemic chemotherapy for lung cancer, with at least one measurable lesion, and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 participated. Before randomisation, patients entered an induction phase which consisted of four cycles of induction pemetrexed (500 mg/m 2) plus cisplatin (75 mg/m 2) on day 1 of a 21-day cycle. Patients who did not progress after completion of four cycles of induction and who had an ECOG performance status of 0 or 1 were stratified according to disease stage (IIIB or IV), ECOG performance status (0 or 1), and induction response (complete or partial response, or stable disease), and randomly assigned (2:1 ratio) to receive maintenance therapy with either pemetrexed (500 mg/m 2 every 21 days) plus best supportive care or placebo plus best supportive care until disease progression. Randomisation was done with the Pocock and Simon minimisation method. Patients and investigators were masked to treatment assignment. The primary endpoint was progression-free survival in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT00789373. Findings: Of the 1022 patients enrolled, 939 participated in the induction phase. Of these, 539 patients were randomly assigned to receive continuation maintenance with pemetrexed plus best supportive care (n=359) or with placebo plus best supportive care (n=180). Among the 359 patients randomised to continuation maintenance with pemetrexed, there was a significant reduction in the risk of disease progression over the placebo group (HR 0·62, 95% CI 0·49-0·79; p<0·0001). The median progression-free survival, measured from randomisation, was 4·1 months (95% CI 3·2-4·6) for pemetrexed and 2·8 months (2·6-3·1) for placebo. Possibly treatment-related laboratory grade 3-4 adverse events were more common in the pemetrexed group (33 [9%] of 359 patients) than in the placebo group (one [<1%] of 180 patients; p<0·0001), as were non-laboratory grade 3-5 adverse events (32 [9%] of 359 patients in the pemetrexed group; eight [4%] of 180 patients in the placebo group; p=0·080); one possibly treatment-related death was reported in each group. The most common adverse events of grade 3-4 in the pemetrexed group were anaemia (16 [4%] of 359 patients), neutropenia (13 [4%]), and fatigue (15 [4%]). In the placebo group, these adverse events were less common: anaemia (one [<1%] of 180 patients), neutropenia (none), and fatigue (one <1%]). The most frequent serious adverse events were anaemia (eight [2%] of 359 patients in the pemetrexed group vs none in the placebo group) and febrile neutropenia (five [1%] vs none). Discontinuations due to drug-related adverse events occurred in 19 (5%) patients in the pemetrexed group and six (3%) patients in the placebo group. Interpretation: Continuation maintenance with pemetrexed is an effective and well tolerated treatment option for patients with advanced non-squamous NSCLC with good performance status who have not progressed after induction therapy with pemetrexed plus cisplatin. Funding: Eli Lilly and Company. © 2012 Elsevier Ltd.


Waschki B.,Hospital Grosshansdorf | Kirsten A.,Hospital Grosshansdorf | Holz O.,Hospital Grosshansdorf Center for Pneumology and Thoracic Surgery | Muller K.-C.,Hospital Grosshansdorf Center for Pneumology and Thoracic Surgery | And 3 more authors.
Chest | Year: 2011

Background: Systemic effects of COPD are incompletely reflected by established prognostic assessments. We determined the prognostic value of objectively measured physical activity in comparison with established predictors of mortality and evaluated the prognostic value of noninvasive assessments of cardiovascular status, biomarkers of systemic inflammation, and adipokines. Methods: In a prospective cohort study of 170 outpatients with stable COPD (mean FEV1, 56% predicted), we assessed lung function by spirometry and body plethysmography; physical activity level (PAL) by a multisensory armband; exercise capacity by 6-min walk distance test; cardiovascular status by echocardiography, vascular Doppler sonography (ankle-brachial index [ABI]), and N-terminal pro-B-type natriuretic peptide level; nutritional and muscular status by BMI and fat-free mass index; biomarkers by levels of high-sensitivity C-reactive protein, IL-6, fibrinogen, adiponectin, and leptin; and health status, dyspnea, and depressive symptoms by questionnaire. Established prognostic indices were calculated. The median follow-up was 48 months (range, 10-53 months). Results: All-cause mortality was 15.4%. After adjustments, each 0.14 increase in PAL was associated with a lower risk of death (hazard ratio [HR], 0.46; 95% CI, 0.33-0.64; P < .001). Compared with established predictors, PAL showed the best discriminative properties for 4-year survival (C statistic, 0.81) and was associated with the highest relative risk of death per standardized decrease. Novel predictors of mortality were adiponectin level (HR, 1.34; 95% CI, 1.06-1.71; P = .017), leptin level (HR, 0.81; 95% CI, 0.65-0.99; P = .042), right ventricular function (Tei-index) (HR, 1.26; 95% CI, 1.04-1.54; P = .020), and ABI < 1.00 (HR, 3.87; 95% CI, 1.44-10.40; P = .007). A stepwise Cox regression revealed that the best model of independent predictors was PAL, adiponectin level, and ABI. The composite of these factors further improved the discriminative properties (C statistic, 0.85). Conclusions: We found that objectively measured physical activity is the strongest predictor of all-cause mortality in patients with COPD. In addition, adiponectin level and vascular status provide independent prognostic information in our cohort. © 2011 American College of Chest Physicians.


Reck M.,Hospital Grosshansdorf
Expert Opinion on Investigational Drugs | Year: 2010

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. Areas covered in this review: This expert review will briefly discuss several antiangiogenic agents approved for the treatment of NSCLC, including many more currently being investigated in clinical trials, such as neutralizing antibodies of pro-angiogenic factors and inhibitors of their tyrosine kinase receptors. This review will also provide an overview of BIBF 1120, a novel, potent, triple angiokinase inhibitor that simultaneously acts on three receptor families involved in blood vessel formation: vascular endothelial growth factor receptors, platelet-derived growth factor receptors and fibroblast growth factor receptors. What the reader will gain: Expert opinion on the promising results obtained in Phase I studies demonstrating that BIBF 1120 is well tolerated in patients with advanced solid tumors will be provided. Further experience from a Phase II monotherapy trial also indicates promising efficacy and a favorable safety profile in patients with relapsed advanced NSCLC. Take home message: Based on these data, the BIBF 1120 Phase III clinical development program is currently underway and will be discussed in further detail. © 2010 Informa UK Ltd.


Soria J.-C.,French Institute of Health and Medical Research | Mauguen A.,Institute Gustave Roussy | Reck M.,Hospital Grosshansdorf | Sandler A.B.,Oregon Health And Science University | And 6 more authors.
Annals of Oncology | Year: 2013

Background: Previous studies have demonstrated the efficacy and safety of bevacizumab in the treatment of non-small-cell lung cancer (NSCLC).Methods: Summary data from randomised trials comparing first-line bevacizumab plus platinum-based chemotherapy with chemotherapy alone for inoperable locally advanced, recurrent or metastatic NSCLC were meta-analysed. Pooled hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), and pooled odds ratio (OR) for adverse events were calculated. The chi-squared tests evaluated interactions between treatment effects, and prognostic factors and patient characteristics. Results: Data of 2194 patients (1313 bevacizumab; 881 controls) from four phase II and III trials: AVF-0757g, JO19907, ECOG 4599 and AVAiL, were analysed. Compared with chemotherapy alone, bevacizumab significantly prolonged OS (HR 0.90; 95% confidence interval [CI] 0.81, 0.99; P = 0.03), and PFS (0.72; 95% CI 0.66, 0.79; P≤0.001). Bevacizumab showed a significantly greater effect on OS in patients with adenocarcinoma versus other histologies (P = 0.02), and patients with body weight loss ≤5% versus >5% (P = 0.03). Bevacizumab significantly increased the risk of grade ≥3 proteinuria, hypertension, haemorrhagic events, neutropenia, and febrile neutropenia. Conclusions: Bevacizumab significantly prolonged OS and PFS when added to first-line platinum-based chemotherapy in patients with advanced NSCLC; no unexpected toxicity was evident. © The Author 2012. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.


Von Leupoldt A.,University of Hamburg | Taube K.,Atem Reha GmbH | Lehmann K.,Atem Reha GmbH | Fritzsche A.,University of Hamburg | Magnussen H.,Hospital Grosshansdorf
Chest | Year: 2011

Background: Anxiety and depression are prevalent comorbidities in COPD and are related to a worse course of disease. The present study examined the impact of anxiety and depression on functional performance, dyspnea, and quality of life (QoL) in patients with COPD at the start and end of an outpatient pulmonary rehabilitation (PR) program. Methods: Before and after PR, 238 patients with COPD (mean FEV 1 % predicted = 54, mean age = 62 years) underwent a 6-min walking test (6MWT). In addition, anxiety, depression, QoL, and dyspnea at rest, after the 6MWT, and during activities were measured. Results: Except for dyspnea at rest, improvements were observed in all outcome measures after PR. Multiple regression analyses showed that before and after PR, anxiety and depression were significantly associated with greater dyspnea after the 6MWT and during activities and with reduced QoL, even after controlling for the effects of age, sex, lung function, and smoking status. Moreover, before and after PR, anxiety was related to greater dyspnea at rest, whereas depression was significantly associated with reduced functional performance in the 6MWT. Conclusions: This study demonstrates that anxiety and depression are significantly associated with increased dyspnea and reduced functional performance and QoL in patients with COPD. These negative associations remain stable over the course of PR, even when improvements in these outcomes are achieved during PR. The results underline the clinical importance of detecting and treating anxiety and depression in patients with COPD. © 2011 American College of Chest Physicians.


Reck M.,Hospital Grosshansdorf
Expert Review of Anticancer Therapy | Year: 2010

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. In this article, these results are discussed in the context of other recently reported studies of EGFR mutation-positive patients in both Asian and non-Asian countries. Furthermore, the clinical implications and future challenges for gefitinib are highlighted. © 2010 Expert Reviews Ltd.


Lung cancer is the leading cause of cancer-related mortality worldwide, with non-small-cell lung cancer (NSCLC) accounting for approximately 85% of all cases. Most patients with NSCLC are diagnosed at an advanced stage and have a poor prognosis, with a 5-year survival rate of <5%. Despite the introduction of new chemotherapeutic agents and molecularly targeted drugs, outcomes remain poor, emphasising the need for new treatment approaches. Inducing or potentiating immune responses via immunotherapeutic manipulation is a viable treatment approach for lung cancer. Antigen-specific, tumour-cell, and dendritic cell-based vaccines have all been evaluated in lung cancer, and some have shown promising clinical activity in phase II trials. These include liposomal BLP25 vaccine (L-BLP25), which targets mucin 1, and melanoma-associated antigen 3 (MAGE-A3) antigen-specific cancer immunotherapeutic (ASCI), which targets MAGE-A3, a peptide expressed almost exclusively on tumour cells. MAGE-A3 ASCI is being evaluated in the adjuvant setting in a phase III trial of patients with early-stage NSCLC, while a phase III trial of L-BLP25 is enrolling patients with unresectable stage III NSCLC. T-cell modulating agents (e.g. antibodies against programmed death 1 and cytotoxic T-lymphocyte-associated antigen-4 [CTLA-4]) are also being investigated. For example, in patients with NSCLC treated with paclitaxel and carboplatin, the phased administration of ipilimumab (an antibody against CTLA-4) resulted in substantial improvements in immune-related progression-free survival compared with chemotherapy alone (5.7 versus 4.6 months; P = 0.05). Immunotherapy in lung cancer is starting to deliver promising results in clinical trials. However, further research will be required to establish the optimal timing of therapy (i.e. in the adjuvant or metastatic settings). In addition, it will be important to determine if immunotherapies are most effective when used alone or in combination with other agents. © The Author 2012. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.


Reck M.,Hospital Grosshansdorf
Targeted Oncology | Year: 2010

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. In addition, small-molecule tyrosine kinase inhibitors are currently in clinical practice or development in several indications. The potential clinical benefit of antiangiogenic agents is accompanied by the need to understand their safety profiles, seek suitable combination regimens and identify patients able to tolerate one treatment over another. This is particularly relevant in cancers for which patients often present with advanced disease and suffer co-morbidities, requiring an agent that is both efficacious and well tolerated over long-term continuous treatment. Using literature from peer-reviewed journals, this review considers different antiangiogenic agents and their safety profiles, focusing on the potential impact of these data on the treatment of patients with NSCLC. © Springer-Verlag 2010.


Heigener D.F.,Hospital Grosshansdorf | Reck M.,Hospital Grosshansdorf
Advances in Therapy | Year: 2011

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. © 2010 Springer Healthcare.

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