Cornely O.A.,University of Cologne |
Cornely O.A.,Center for Integrated Oncology Cologne Bonn |
Vehreschild J.J.,University of Cologne |
Vehreschild M.J.G.T.,University of Cologne |
And 16 more authors.
Antimicrobial Agents and Chemotherapy | Year: 2011
Our objective was to evaluate the maximum tolerated dose of caspofungin for invasive aspergillosis (IA). The safety and pharmacokinetics of escalating dosages of caspofungin were investigated in IA. Eight patients each received caspofungin 70, 100, 150, or 200 mg once a day (QD). Dose-limiting toxicity (DLT) was defined as the same non-hematological treatment-related adverse event of grade ≥4 in 2 of 8 patients or ≥3 in 4 of 8 patients in a cohort. A total of 46 patients (median age, 61 years; 21 female; 89% with hematological malignancies) received caspofungin (9, 8, 9, and 20 patients in the 70-, 100-, 150-, and 200-mg cohorts) for a median of 24.5 days. Plasma pharmacokinetics were linear across the investigated dosages and followed a two-compartment model, with weight as the covariate on clearance and sex as the covariate on central volume of distribution. Simulated peak plasma concentrations at steady state ranged from 14.2 to 40.6 mg/liter (28%), trough concentrations from 4.1 to 11.8 mg/liter (58%), and area under the concentration-time curve from 175 to 500 mg/liter/h (32%) (geometric mean, geometric coefficient of variation). Treatment was well tolerated without dose-limiting toxicity. The rate of complete or partial responses was 54.3%, and the overall mortality at 12-week follow-up was 28.3%. In first-line treatment of invasive aspergillosis, daily doses of up to 200 mg caspofungin were well tolerated and the maximum tolerated dose was not reached. Pharmacokinetics was linear. Response rates were similar to those previously reported for voriconazole and liposomal amphotericin. Copyright © 2011, American Society for Microbiology. All Rights Reserved.
Simon S.T.,University of Cologne |
Simon S.T.,Center for Integrated Oncology Cologne Bonn |
Weingartner V.,University of Cologne |
Higginson I.J.,King's College London |
And 4 more authors.
Journal of Pain and Symptom Management | Year: 2014
Context Episodic breathlessness is a common and distressing symptom in patients with advanced disease. Still, it is not yet clearly defined. Objectives The aim of this work was to develop an international definition, categorization, and terminology of episodic breathlessness. Methods An online Delphi survey was conducted with international breathlessness experts. We used a structured questionnaire to identify specific aspects and reach agreement on a definition, categorization, and terminology (five-point Likert scale). Consensus was defined in advance as ≤70% agreement. Results Thirty-one of 68 (45.6%), 29 of 67 (43.3%), and 33 of 67 (49.3%) experts responded in the first, second, and third rounds, respectively. Participants were 20-79 years old, about 60% male, and more than 75% rated their own breathlessness expertise as moderate to high. After three rounds, consensus was reached on a definition, categorization, and terminology (84.4%, 96.3%, and 92.9% agreement). The final definition includes general and qualitative aspects of the symptom, for example, time-limited severe worsening of intensity or unpleasantness of breathlessness in the patient's perception. Categories are predictable or unpredictable, depending on whether any triggers can be identified. Conclusion There is high agreement on clinical and operational aspects of episodic breathlessness in advanced disease among international experts. The consented definition and categorization may serve as a catalyst for clinical and basic research to improve symptom control and patients' quality of life. © 2014 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.
Verweij P.E.,Radboud University Nijmegen |
Ananda-Rajah M.,General Medicine and Infectious Diseases Units |
Andes D.,University of Wisconsin - Madison |
Arendrup M.C.,Statens Serum Institute |
And 18 more authors.
Drug Resistance Updates | Year: 2015
An international expert panel was convened to deliberate the management of azole-resistant aspergillosis. In culture-positive cases, in vitro susceptibility testing should always be performed if antifungal therapy is intended. Different patterns of resistance are seen, with multi-azole and pan-azole resistance more common than resistance to a single triazole. In confirmed invasive pulmonary aspergillosis due to an azole-resistant Aspergillus, the experts recommended a switch from voriconazole to liposomal amphotericin B (L-AmB; Ambisome®). In regions with environmental resistance rates of ≥10%, a voriconazole-echinocandin combination or L-AmB were favoured as initial therapy. All experts recommended L-AmB as core therapy for central nervous system aspergillosis suspected to be due to an azole-resistant Aspergillus, and considered the addition of a second agent with the majority favouring flucytosine. Intravenous therapy with either micafungin or L-AmB given as either intermittent or continuous therapy was recommended for chronic pulmonary aspergillosis due to a pan-azole-resistant Aspergillus. Local and national surveillance with identification of clinical and environmental resistance patterns, rapid diagnostics, better quality clinical outcome data, and a greater understanding of the factors driving or minimising environmental resistance are areas where research is urgently needed, as well as the development of new oral agents outside the azole drug class. © 2015 The Authors.
PubMed | University of Barcelona, University of Ulm, Bethanien Hospital, Johanniter Hospital and 10 more.
Type: Journal Article | Journal: Oncotarget | Year: 2015
While recent data show that crizotinib is highly effective in patients with ROS1 rearrangement, few data is available about the prognostic impact, the predictive value for different treatments, and the genetic heterogeneity of ROS1-positive patients.1137 patients with adenocarcinoma of the lung were analyzed regarding their ROS1 status. In positive cases, next-generation sequencing (NGS) was performed. Clinical characteristics, treatments and outcome of these patients were assessed. Overall survival (OS) was compared with genetically defined subgroups of ROS1-negative patients.19 patients of 1035 evaluable (1.8%) had ROS1-rearrangement. The median OS has not been reached. Stage IV patients with ROS1-rearrangement had the best OS of all subgroups (36.7 months, p < 0.001). 9 of 14 (64.2%) patients had at least one response to chemotherapy. Estimated mean OS for patients receiving chemotherapy and crizotinib was 5.3 years. Ten patients with ROS1-rearrangement (52.6%) harbored additional aberrations.ROS1-rearangement is not only a predictive marker for response to crizotinib, but also seems to be the one of the best prognostic molecular markers in NSCLC reported so far. In stage IV patients, response to chemotherapy was remarkable high and overall survival was significantly better compared to other subgroups including EGFR-mutated and ALK-fusion-positive NSCLC.
Schultheis A.M.,University of Cologne |
Schultheis A.M.,Center for Integrated Oncology Cologne Bonn |
Bos M.,Center for Integrated Oncology Cologne Bonn |
Bos M.,University of Cologne |
And 11 more authors.
Modern Pathology | Year: 2014
Small-cell lung cancer (SCLC) comprises about 13-15% of all lung cancers, and more than 29 400 new cases have been diagnosed in the United States in the year 2012. SCLC is a biologically complex tumor typically occurring in heavy smokers. Its medical treatment has almost remained unchanged over the last decades and selected treatment options have not been established so far, mainly due to the lack of targetable genetic alterations. In this study we analyzed a cohort of 307 SCLC samples for fibroblast growth factor receptor 1 (FGFR1) amplification using a dual color FISH probe. FGFR1 status was correlated with clinical data. FGFR1 amplifications were observed in 5.6% of evaluable pulmonary SCLCs. Most of them (93%) fulfilled the criteria for high-level amplification and only one case showed low-level amplification. Amplification patterns were homogenous in the entire tumor area without occurrence of any 'hot spot' areas. FGFR1 amplification status was not associated with age, sex, stage, smoking status or overall survival. FGFR1 amplification analysis by FISH analysis in SCLC is, under respect of certain technical issues, applicable in the routine clinical setting. However, the FGFR1 amplification patterns in SCLC differs strongly from the previously described FGFR1 amplification pattern in squamous cell carcinoma of the lung, as positive SCLC harbor mostly homogeneous high-level amplifications. We provide evidence that an estimated number of 1640 newly diagnosed FGFR1-positive SCLC cases in the United States annually could benefit from targeted therapy. Therefore, we recommend including SCLC in the screening for ongoing clinical trials with FGFR1 inhibitors.
Buecken R.,University of Cologne |
Galushko M.,University of Cologne |
Golla H.,University of Cologne |
Strupp J.,University of Cologne |
And 6 more authors.
Patient Education and Counseling | Year: 2012
Objective: Investigate multiple sclerosis patients' desire to communicate with their physicians about their disease progression and end-of-life issues. Methods: Persons meeting the inclusion criteria of feeling severely affected by MS were invited via the German MS society to complete a needs questionnaire. Replies to questions on physician empathy and wishes about communication regarding disease progression and death and dying were quantitatively analyzed. Endpoints (point 1 + 2/4 + 5) of 5-point-likert scales are summarized under results. Results: 573 of 867 questionnaires meeting our criteria were analyzed. In response to a general question 64% (n=358) indicated a wish for disease progression and death and dying to be addressed by their doctor. A majority (76%, n=427) considered it important that progression of their disease be discussed, while 44% (n=246) regard addressing death and dying as unimportant. No objective disease criteria could be identified to explain the wish for communicating end-of-life issues. Doctors who were retrospectively viewed as avoiding raising critical aspects of the illness were perceived as less empathetic (p<0.001). Conclusion: People with MS have a desire to talk about progression of their disease with their doctors. Practice implications: Physicians should be empathetic in raising critical aspects of the patients' illness individually. © 2012 Elsevier Ireland Ltd.
Koppitz H.,University of Bonn |
Rockstroh J.K.,University of Bonn |
Schuller H.,University of Bonn |
Standop J.,University of Bonn |
And 3 more authors.
Cancer Treatment Reviews | Year: 2012
Thymomas are the most common tumors of the anterior mediastinum. Classification, treatment options and understanding of the pathophysiology of thymoma have changed over the past years. It is hoped that novel therapeutic strategies will lead to a survival benefit in these patients. It has turned out that patients with thymoma are best treated with multimodality therapy. In this review, a pathologist, an immunologist, a surgeon, a radiotherapist, a pneumologist and oncologists discuss the current status of classification and strategies for the treatment of thymoma patients. © 2011 Elsevier Ltd.
Kloth M.,University of Cologne |
Kloth M.,Center for Integrated Oncology Cologne Bonn |
Buettner R.,University of Cologne |
Buettner R.,Center for Integrated Oncology Cologne Bonn
Genes | Year: 2014
Traditionally, tumors are classified by histopathological criteria, i.e., based on their specific morphological appearances. Consequently, current therapeutic decisions in oncology are strongly influenced by histology rather than underlying molecular or genomic aberrations. The increase of information on molecular changes however, enabled by the Human Genome Project and the International Cancer Genome Consortium as well as the manifold advances in molecular biology and high-throughput sequencing techniques, inaugurated the integration of genomic information into disease classification. Furthermore, in some cases it became evident that former classifications needed major revision and adaption. Such adaptations are often required by understanding the pathogenesis of a disease from a specific molecular alteration, using this molecular driver for targeted and highly effective therapies. Altogether, reclassifications should lead to higher information content of the underlying diagnoses, reflecting their molecular pathogenesis and resulting in optimized and individual therapeutic decisions. The objective of this article is to summarize some particularly important examples of genome-based classification approaches and associated therapeutic concepts. In addition to reviewing disease specific markers, we focus on potentially therapeutic or predictive markers and the relevance of molecular diagnostics in disease monitoring. © 2014 by the authors; licensee MDPI, Basel, Switzerland.
Strupp J.,University of Cologne |
Hartwig A.,University of Cologne |
Golla H.,University of Cologne |
Galushko M.,University of Cologne |
And 4 more authors.
Palliative Medicine | Year: 2012
Background: The situation for people feeling severely affected by Multiple Sclerosis (MS) remains largely unexamined and the term 'esevere MSf is not clearly defined. Aim: Our study describes this sub-group of patients utilizing exclusively a subjective inclusion criterion to analyse their reasons for feeling severely affected and document their perceived unmet needs. Design: A questionnaire with open- and closed-ended items addressing only patients feeling severely affected was sent out nationwide. Expanded Disability Status Score (EDSS) and subjectively severe affectedness were analysed for correlation. After dichotomizing both scores by a median split, the answers were allocated to these groups and tested for significant differences. Setting/participants: 1,110 questionnaires were analysed regarding the closed-ended questions while a subsample of 40% (n = 445) was analysed regarding the open-ended questions. Average age of participants was 51.87 years. Average time since diagnosis was 16.6 years. Main course of the disease was secondary progressive (35.5%). Results: The most frequently mentioned reasons for feeling severely affected were lack of mobility (56.4%) and fatigue (27.4%). Significant percentages for unmet needs were seen in the categories of funding services (31.0%), better social integration (24.7%) and medical support (25.2%). A significant correlation was observed between EDSS and subjectively felt affectedness (p ≤ 0.01). Motor disorders explained differences in patient needs behind a higher EDSS score; higher severe affectedness referred to other issues like dependency and immobility. Conclusions: EDSS is insufficient for usage as the sole instrument for measuring severe affectedness as it does not take into account other potential reasons. Complex patient needs necessitate multi-professional care as offered by palliative medicine. © 2012 The Author(s).
Schweer K.E.,Universitatsklinikum Cologne |
Wittersheim M.,Universitatsklinikum Cologne |
Bangard C.,Universitatsklinikum Cologne |
Frank K.F.,Universitatsklinikum Cologne |
Cornely O.A.,Center for Integrated Oncology Cologne Bonn
Deutsche Medizinische Wochenschrift | Year: 2014
Chronic pulmonary aspergillosis (CPA) is a rare complication in patients with either mild immunosuppression or various pulmonary diseases. Diagnosis and therapy are challenging because of unspecific symptoms like productive cough, weight loss, fever and haemoptysis. Differential diagnoses are manifold, and CPA is characterized by findings in chest CT and serologic proof of precipitins. Surgery is only recommended for simple aspergillomas. Recurrent prolonged courses of antifungal treatment yield satisfactory short-term outcome, but long-term prognosis is uncertain. We provide an overview of the literature and present four cases to illustrate disease diversity. © 2014 Georg Thieme Verlag KG Stuttgart New York.