Essen, Germany
Essen, Germany

Time filter

Source Type

Eberhardt W.E.E.,West German Cancer Center | Gauler T.C.,West German Cancer Center | LePechoux C.,Institute Gustave Roussy | Stamatis G.,Ruhrlandclinic | And 11 more authors.
Lung Cancer | Year: 2013

Background: Induction chemoradiotherapy plus surgery remains an option to study in IIIA(N2) and selected IIIB NSCLC. Here we report ten-year long-term survival of a prospective multicenter German-French phase-II trial with trimodality. Patients and methods: Mediastinoscopically proven IIIA(N2)/selected IIIB NSCLC received three cycles cisplatin (50mg/m2 day 1+8) and paclitaxel (175mg/m2d1) qd 22. Concurrent CTx/RTx followed: 45Gy (1.5Gy bid) with cisplatin 50mg/m2 day 2+9 and etoposide 100mg/m2 d 4-6. Surgery was planned three to five weeks after RTx. If evaluated inoperable/irresectable at the end of RTx, definitive RTx-boost (20Gy; 2Gy qd) followed. Here we report 10-year-LTS for this cohort. Results: All 64 patients were accrued 3/99 to 2/02. Patients characteristics: IIIA(N2)/IIIB 25/39; m/f 48/16; adeno/squamous/large-cell/adenosquamous/NOS 15/26/18/3/2; age: median 52.5 (range 33-69). 36 operated: R0 32/36 (89%); pCR 16/36 (44%). 10-year-LTS%; all 26.0; IIIA(N2) 37.1; IIIB 17.9; relevant prognostic factors (exploratory): pretreatment - histopathology (squamous/adeno) - age (<50/≥50) - Charlson-CI: 1/>1 - BMI (≥25/<25) - pack years smoking (≥10/<10); treatment-dependent - R0/no-R0. Conclusions: This regimen achieves substantial LTS. Interestingly, adenocarcinomas, older patients, unfavorable comorbidity scores, higher BMI and light smokers demonstrate poor long-term outcome even with aggressive trimodality. This dataset defines the rationale for our ongoing randomized trial with surgery after induction therapy in IIIA(N2)/selected IIIB (ESPATÜ). © 2013.


News Article | February 27, 2017
Site: www.eurekalert.org

(PRINCETON, N.J., Feb. 27, 2017) - Bristol-Myers Squibb Company (NYSE:BMY) today announced that Columbia University Medical Center and Peter MacCallum Cancer Centre (Peter Mac) have joined the International Immuno-Oncology Network (II-ON), a global peer-to-peer collaboration between Bristol-Myers Squibb and academia that aims to advance Immuno-Oncology (I-O) science and translational medicine to improve patient outcomes. Launched in 2012 by Bristol-Myers Squibb, the II-ON was one of the first networks to bring academia and industry together to further the scientific understanding of I-O, and has expanded from 10 to 15 sites including more than 250 investigators working on over 150 projects across 20 tumor types. The II-ON has generated cutting-edge I-O data that have informed the development of new I-O agents, yielded publications and produced some of the earliest findings on a variety of biomarkers and target identification and validation. "Bristol-Myers Squibb has long believed the future of cancer research is dependent on investments in science and partnerships. We formed the II-ON to facilitate innovation in I-O science and drug discovery by providing a streamlined framework for peer-to-peer collaboration among global cancer research leaders," said Nils Lonberg, Head of Oncology Biology Discovery at Bristol-Myers Squibb. "The significant discoveries generated by the II-ON over the past five years have not only informed our robust early I-O pipeline, but also serve to advance the entire field. We are proud to collaborate with Columbia University Medical Center and Peter Mac, and together with the entire II-ON will continue to lead pioneering research and heighten our collective understanding of the science behind I-O." Through the II-ON, Bristol-Myers Squibb is collaborating with leading cancer research institutions around the world to generate innovative I-O science, launch biology-driven trials and seek out cutting-edge technologies with the goal of translating research findings into clinical trials and, ultimately, clinical practice. "I-O research may be transforming the way we treat cancer," said Charles G. Drake, MD, PhD, Professor of Medicine at Columbia University Medical Center and Director of Genitourinary Oncology and Associate Director for Clinical Research at the Herbert Irving Comprehensive Cancer Center at New York-Presbyterian/Columbia. "The II-ON offers a tremendous opportunity to work smarter and faster along with our colleagues to address fundamental scientific questions in I-O." "We believe the collective knowledge and research power of the II-ON will generate groundbreaking findings in I-O with the potential to improve outcomes for people affected by cancer," said Professor Joe Trapani, Executive Director Cancer Research and Head of the Cancer Immunology Program at Peter MacCallum Cancer Centre, Melbourne, Australia. Building on the success of the II-ON, Bristol-Myers Squibb has invested in several other models of scientific collaboration with academic partners across the globe, including the Global Expert Centers Initiative (GECI) and the Immuno-Oncology Integrated Community Oncology Network (IO-ICON). "We believe a one-size-fits-all research approach does not facilitate innovation," said Lonberg. "Our tailored collaborations with academic centers expand our research capabilities and accelerate our collective ability to deliver potentially life-changing results for patients." The II-ON, formed in 2012, is a global peer-to-peer collaboration between Bristol-Myers Squibb and academia advancing the science of Immuno-Oncology (I-O) through a series of preclinical, translational and biology-focused research objectives. The research in the collaboration is focused on three fundamental scientific pillars: understanding the mechanisms of resistance to immunotherapy; identifying patient populations likely to benefit from immunotherapy; and exploring novel combination therapies that may enhance anti-tumor response through complementary mechanisms of action. The II-ON facilitates the translation of scientific research findings into drug discovery and development, with the goal of introducing new treatment options into clinical practice. In addition to Bristol-Myers Squibb, the II-ON currently comprises 15 leading cancer research institutions, including: Clinica Universidad Navarra, Dana-Farber Cancer Institute, The Earle A. Chiles Research Institute (Providence Health & Services), Institut Gustave Roussy, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione G. Pascale", Bloomberg-Kimmel Institute for Cancer Immunotherapy at the Johns Hopkins Kimmel Cancer Center, Memorial Sloan Kettering Cancer Center, National Cancer Center Japan, The Netherlands Cancer Institute, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, University College London, The University of Chicago, West German Cancer Center/University Hospital Essen, and now Columbia University Medical Center and Peter MacCallum Cancer Centre. Bristol-Myers Squibb: At the Forefront of Immuno-Oncology Science & Innovation At Bristol-Myers Squibb, patients are at the center of everything we do. Our vision for the future of cancer care is focused on researching and developing transformational Immuno-Oncology (I-O) medicines that will raise survival expectations in hard-to-treat cancers and will change the way patients live with cancer. We are leading the scientific understanding of I-O through our extensive portfolio of investigational and approved agents - including the first combination of two I-O agents in metastatic melanoma - and our differentiated clinical development program, which is studying broad patient populations across more than 20 types of cancers with 12 clinical-stage molecules designed to target different immune system pathways. Our deep expertise and innovative clinical trial designs uniquely position us to advance the science of combinations across multiple tumors and potentially deliver the next wave of I-O combination regimens with a sense of urgency. We also continue to pioneer research that will help facilitate a deeper understanding of the role of immune biomarkers and inform which patients will benefit most from I-O therapies. We understand making the promise of I-O a reality for the many patients who may benefit from these therapies requires not only innovation on our part, but also close collaboration with leading experts in the field. Our partnerships with academia, government, advocacy and biotech companies support our collective goal of providing new treatment options to advance the standards of clinical practice. Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol-Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube and Facebook. This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding the research, development and commercialization of pharmaceutical products. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Bristol-Myers Squibb's business, particularly those identified in the cautionary factors discussion in Bristol-Myers Squibb's Annual Report on Form 10-K for the year ended December 31, 2016 in our Quarterly Reports on Form 10-Q and our Current Reports on Form 8-K. Bristol-Myers Squibb undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise.


PRINCETON, N.J.--(BUSINESS WIRE)--Bristol-Myers Squibb Company (NYSE:BMY) today announced that Columbia University Medical Center and Peter MacCallum Cancer Centre (Peter Mac) have joined the International Immuno-Oncology Network (II-ON), a global peer-to-peer collaboration between Bristol-Myers Squibb and academia that aims to advance Immuno-Oncology (I-O) science and translational medicine to improve patient outcomes. Launched in 2012 by Bristol-Myers Squibb, the II-ON was one of the first networks to bring academia and industry together to further the scientific understanding of I-O, and has expanded from 10 to 15 sites including more than 250 investigators working on over 150 projects across 20 tumor types. The II-ON has generated cutting-edge I-O data that have informed the development of new I-O agents, yielded publications and produced some of the earliest findings on a variety of biomarkers and target identification and validation. “Bristol-Myers Squibb has long believed the future of cancer research is dependent on investments in science and partnerships. We formed the II-ON to facilitate innovation in I-O science and drug discovery by providing a streamlined framework for peer-to-peer collaboration among global cancer research leaders,” said Nils Lonberg, Head of Oncology Biology Discovery at Bristol-Myers Squibb. “The significant discoveries generated by the II-ON over the past five years have not only informed our robust early I-O pipeline, but also serve to advance the entire field. We are proud to collaborate with Columbia University Medical Center and Peter Mac, and together with the entire II-ON will continue to lead pioneering research and heighten our collective understanding of the science behind I-O.” Through the II-ON, Bristol-Myers Squibb is collaborating with leading cancer research institutions around the world to generate innovative I-O science, launch biology-driven trials and seek out cutting-edge technologies with the goal of translating research findings into clinical trials and, ultimately, clinical practice. “I-O research may be transforming the way we treat cancer,” said Charles G. Drake, MD, PhD, Professor of Medicine at Columbia University Medical Center and Director of Genitourinary Oncology and Associate Director for Clinical Research at the Herbert Irving Comprehensive Cancer Center at New York-Presbyterian/Columbia. “The II-ON offers a tremendous opportunity to work smarter and faster along with our colleagues to address fundamental scientific questions in I-O.” “We believe the collective knowledge and research power of the II-ON will generate groundbreaking findings in I-O with the potential to improve outcomes for people affected by cancer,” said Professor Joe Trapani, Executive Director Cancer Research and Head of the Cancer Immunology Program at Peter MacCallum Cancer Centre, Melbourne, Australia. Building on the success of the II-ON, Bristol-Myers Squibb has invested in several other models of scientific collaboration with academic partners across the globe, including the Global Expert Centers Initiative (GECI) and the Immuno-Oncology Integrated Community Oncology Network (IO-ICON). "We believe a one-size-fits-all research approach does not facilitate innovation,” said Lonberg. “Our tailored collaborations with academic centers expand our research capabilities and accelerate our collective ability to deliver potentially life-changing results for patients." The II-ON, formed in 2012, is a global peer-to-peer collaboration between Bristol-Myers Squibb and academia advancing the science of Immuno-Oncology (I-O) through a series of preclinical, translational and biology-focused research objectives. The research in the collaboration is focused on three fundamental scientific pillars: understanding the mechanisms of resistance to immunotherapy; identifying patient populations likely to benefit from immunotherapy; and exploring novel combination therapies that may enhance anti-tumor response through complementary mechanisms of action. The II-ON facilitates the translation of scientific research findings into drug discovery and development, with the goal of introducing new treatment options into clinical practice. In addition to Bristol-Myers Squibb, the II-ON currently comprises 15 leading cancer research institutions, including: Clinica Universidad Navarra, Dana-Farber Cancer Institute, The Earle A. Chiles Research Institute (Providence Health & Services), Institut Gustave Roussy, Istituto Nazionale per lo Studio e la Cura dei Tumori “Fondazione G. Pascale”, Bloomberg-Kimmel Institute for Cancer Immunotherapy at the Johns Hopkins Kimmel Cancer Center, Memorial Sloan Kettering Cancer Center, National Cancer Center Japan, The Netherlands Cancer Institute, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, University College London, The University of Chicago, West German Cancer Center/University Hospital Essen, and now Columbia University Medical Center and Peter MacCallum Cancer Centre. Bristol-Myers Squibb: At the Forefront of Immuno-Oncology Science & Innovation At Bristol-Myers Squibb, patients are at the center of everything we do. Our vision for the future of cancer care is focused on researching and developing transformational Immuno-Oncology (I-O) medicines that will raise survival expectations in hard-to-treat cancers and will change the way patients live with cancer. We are leading the scientific understanding of I-O through our extensive portfolio of investigational and approved agents – including the first combination of two I-O agents in metastatic melanoma – and our differentiated clinical development program, which is studying broad patient populations across more than 20 types of cancers with 12 clinical-stage molecules designed to target different immune system pathways. Our deep expertise and innovative clinical trial designs uniquely position us to advance the science of combinations across multiple tumors and potentially deliver the next wave of I-O combination regimens with a sense of urgency. We also continue to pioneer research that will help facilitate a deeper understanding of the role of immune biomarkers and inform which patients will benefit most from I-O therapies. We understand making the promise of I-O a reality for the many patients who may benefit from these therapies requires not only innovation on our part, but also close collaboration with leading experts in the field. Our partnerships with academia, government, advocacy and biotech companies support our collective goal of providing new treatment options to advance the standards of clinical practice. Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol-Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube and Facebook. This press release contains “forward-looking statements” as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding the research, development and commercialization of pharmaceutical products. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Bristol-Myers Squibb’s business, particularly those identified in the cautionary factors discussion in Bristol-Myers Squibb’s Annual Report on Form 10-K for the year ended December 31, 2016 in our Quarterly Reports on Form 10-Q and our Current Reports on Form 8-K. Bristol-Myers Squibb undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise.


Strumberg D.,Ruhr University Bochum | Scheulen M.E.,West German Cancer Center | Schultheis B.,Ruhr University Bochum | Richly H.,West German Cancer Center | And 7 more authors.
British Journal of Cancer | Year: 2012

Background: In a phase I dose-escalation study, regorafenib demonstrated tolerability and antitumour activity in solid tumour patients. The study was expanded to focus on patients with metastatic colorectal cancer (CRC). Methods: Patients received oral regorafenib 60-220 mg daily (160 mg daily in the extension cohort) in cycles of 21 days on, 7 days off treatment. Assessments included toxicity, response, pharmacokinetics and pharmacodynamics. Results: Thirty-eight patients with heavily pretreated CRC (median 4 prior lines of therapy, range 0-7) were enrolled in the dose-escalation and extension phases; 26 patients received regorafenib 160 mg daily. Median treatment duration was 53 days (range 7-280 days). The most common treatment-related toxicities included hand-foot skin reaction, fatigue, voice change and rash. Twenty-seven patients were evaluable for response: 1 achieved partial response and 19 had stable disease. Median progression-free survival was 107 days (95% CI, 66-161). At steady state, regorafenib and its active metabolites had similar systemic exposure. Pharmacodynamic assessment indicated decreased tumour perfusion in most patients. Conclusion: Regorafenib showed tolerability and antitumour activity in patients with metastatic CRC. This expanded-cohort phase I study provided the foundation for further clinical trials of regorafenib in this patient population. © 2012 Cancer Research UK.


Koldehoff M.,University of Duisburg - Essen | Lindemann M.,Institute for Transfusion Medicine | Opalka B.,West German Cancer Center | Bauer S.,West German Cancer Center | And 2 more authors.
Leukemia and Lymphoma | Year: 2015

Cytomegalovirus (HCMV) reactivation occurs frequently after hematopoietic stem cell transplantation and is associated with an increased treatment-related mortality. Induction of apoptosis by HCMV is unusual because HCMV utilizes various strategies to prevent apoptosis in infected cells in order to delay cell death and maintain viral replication. Here we show that HCMV can infect the acute leukemia cell lines Kasumi-1 (AML) and SD-1 (BCR-ABL-positive ALL), which inhibited their proliferation and induced apoptosis in almost all cells after 14 days. Although HCMV induced a significant up-regulation of the anti-apoptotic gene cFLIP and the anti-stress gene Gadd45a, and simultaneously down-regulated the pro-apoptotic genes p53, Gadd45gamma in Kasumi-1 and SD-1 cells, we found that these anti-apoptotic mechanisms failed in HCMV-infected acute leukemia cells and apoptosis occurred via a caspase-dependent pathway. We conclude that HCMV can provide anti-leukemic effects in vitro. To determine if this phenomenon may be clinically relevant further investigations will be required. © 2015 Informa UK, Ltd.


PubMed | Center Francois Baclesse, Guangdong General Hospital and Guangdong Academy of Medical science, University of Barcelona, Hoffmann-La Roche and 6 more.
Type: | Journal: Lung cancer (Amsterdam, Netherlands) | Year: 2016

Active smokers with non-small-cell lung cancer (NSCLC) have increased erlotinib metabolism versus non-smoking patients, which reduces exposure. Therefore, an increased erlotinib dose may be beneficial. The CurrentS study (NCT01183858) assessed efficacy and safety of 300mg erlotinib (E300) as second-line therapy in current smokers with locally advanced or metastatic NSCLC versus the standard 150mg dose (E150).Patients with stage IIIB/IV NSCLC (current smokers who failed first-line platinum-based chemotherapy) were randomized to receive E150 or E300 until progression/death/unacceptable toxicity.progression-free survival (PFS). Secondary endpoints: overall survival (OS), disease control rate and safety.A total of 342 patients were screened; the intent-to-treat population comprised 159 E300 patients and 154 E150 patients. Median PFS was 7.0 versus 6.9 weeks with E300 versus E150, respectively (unstratified hazard ratio [HR]=1.05, 95% confidence interval [CI]: 0.83-1.33; unstratified log-rank P=0.671). Median OS was 6.8 months in both arms (unstratified HR=1.03, 95% CI: 0.80-1.32; unstratified log-rank P=0.846). Overall, 89.2% (E300 arm) and 84.4% (E150 arm) experienced 1 adverse event (AE) of any grade (44.3% and 37%, respectively, experienced grade 3 AEs); AEs of special interest were reported in 67.7% and 47.4% of patients, respectively. E300 resulted in higher mean plasma concentrations versus E150, however, this did not improve efficacy.Despite the difference in erlotinib exposure, there was no evidence of an incremental efficacy benefit of a higher erlotinib dose versus the standard dose in this population of highly active smokers.


Nel I.,West German Cancer Center | Jehn U.,West German Cancer Center | Gauler T.,University of Duisburg - Essen | Hoffmann A.-C.,West German Cancer Center | Hoffmann A.-C.,University of Duisburg - Essen
Translational Lung Cancer Research | Year: 2014

Background: Circulating tumor cells (CTC) could serve as a "liquid biopsy" for individualizing and monitoring treatment in patients with solid tumors as recently shown by our group. We assessed which nonhematopoietic cell types are identifiable in the peripheral blood of patients with non-small cell lung cancer (NSCLC) and correlated those to clinical characteristics. Methods: Blood from NSCLC patients (n=43) was processed as previously described. For subtype analyses CTC were negatively enriched by hematopoietic cell depletion. The remaining cell suspension included preenriched tumor cells and was spun onto glass slides and further characterized by multi-immunofluorescence staining against epithelial markers pan-cytokeratin (CK) and epithelial cell adhesion molecule (EpCAM), mesenchymal marker N-cadherin, stem cell marker CD133, hematopoietic marker CD45 and nuclear counterstain DAPI. Individual cell type profiles were analyzed and correlated to therapeutic outcome. Results: Among other associations of CTC subtypes with clinical parameters Kaplan-Meier test revealed that an increased CD133-positive to pan-CK-positive cell type ratio (stem cell like to epithelial ratio) and the presence of mesenchymal N-cadherin+ cells, both were significantly associated to shortened PFS (2 vs. 8 months, P=0.003, HR =4.43; 5 vs. 8 months, P=0.03, HR =2.63). Conclusions: Our data suggest that different CTC populations are identifiable in peripheral blood and that these individual cell type profiles might be used to predict outcome to platinum based systemic therapies in lung cancer patients. © Translational lung cancer research. All rights reserved.


PubMed | West German Cancer Center, b Institute for Transfusion Medicine and University of Duisburg - Essen
Type: Journal Article | Journal: Leukemia & lymphoma | Year: 2015

Cytomegalovirus (HCMV) reactivation occurs frequently after hematopoietic stem cell transplantation and is associated with an increased treatment-related mortality. Induction of apoptosis by HCMV is unusual because HCMV utilizes various strategies to prevent apoptosis in infected cells in order to delay cell death and maintain viral replication. Here we show that HCMV can infect the acute leukemia cell lines Kasumi-1 (AML) and SD-1 (BCR-ABL-positive ALL), which inhibited their proliferation and induced apoptosis in almost all cells after 14 days. Although HCMV induced a significant up-regulation of the anti-apoptotic gene cFLIP and the anti-stress gene Gadd45a, and simultaneously down-regulated the pro-apoptotic genes p53, Gadd45gamma in Kasumi-1 and SD-1 cells, we found that these anti-apoptotic mechanisms failed in HCMV-infected acute leukemia cells and apoptosis occurred via a caspase-dependent pathway. We conclude that HCMV can provide anti-leukemic effects in vitro. To determine if this phenomenon may be clinically relevant further investigations will be required.


PubMed | West German Cancer Center
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2016

440 Background: Monoclonal antibodies against the epidermal growth factor receptor (EGFR) have improved treatment options for colorectal cancer (CRC), but tumors harboring RAS mutations are resistant. Full molecular understanding of RAS-mediated protection is key to the development of sensitization strategies.We have used cell culture and murine CRC transplant models to study whether RAS solely imposes resistance by compensating EGFR signaling blockade, or additionally interferes with antibody-dependent cellular cytotoxicity (ADCC).Both clinically approved anti-EGFR antibodies, cetuximab and panitumumab, were equally cytotoxic in CRC cells in vitro. Interestingly, cetuximab, a chimeric IgGRAS-mutant CRCs escape anti-EGFR antibody-mediated receptor blockade as well as ADCC in vivo. Pharmacologic modulation of RAS downstream effectors, such as BCL-XL, can restore sensitivity to antibody effector mechanisms. [Table: see text].

Loading West German Cancer Center collaborators
Loading West German Cancer Center collaborators