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Pancreatic Neoplasms: HELP
Articles by Werner Scheithauer
Based on 13 articles published since 2008
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Between 2008 and 2019, W. Scheithauer wrote the following 13 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Guideline Consensus statement on mandatory measurements in pancreatic cancer trials (COMM-PACT) for systemic treatment of unresectable disease. 2018

Ter Veer, Emil / van Rijssen, L Bengt / Besselink, Marc G / Mali, Rosa M A / Berlin, Jordan D / Boeck, Stefan / Bonnetain, Franck / Chau, Ian / Conroy, Thierry / Van Cutsem, Eric / Deplanque, Gael / Friess, Helmut / Glimelius, Bengt / Goldstein, David / Herrmann, Richard / Labianca, Roberto / Van Laethem, Jean-Luc / Macarulla, Teresa / van der Meer, Jonathan H M / Neoptolemos, John P / Okusaka, Takuji / O'Reilly, Eileen M / Pelzer, Uwe / Philip, Philip A / van der Poel, Marcel J / Reni, Michele / Scheithauer, Werner / Siveke, Jens T / Verslype, Chris / Busch, Olivier R / Wilmink, Johanna W / van Oijen, Martijn G H / van Laarhoven, Hanneke W M. ·Department of Medical Oncology, Cancer Center Amsterdam, Academic Medical Center, Amsterdam, Netherlands. · Department of Surgery, Cancer Center Amsterdam, Academic Medical Center, Amsterdam, Netherlands. · Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, TN, USA. · Department of Internal Medicine III, Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Munich, Germany. · Methodology and Quality of Life in Oncology Unit, University Hospital of Besançon, Besançon, France. · Royal Marsden NHS Foundation Trust, London and Surrey, UK. · Department of Medical Oncology, Institut de Cancérologie de Lorraine and Lorraine University, Vandoeuvre-lès-Nancy, France. · Department of Gastroenterology and Digestive Oncology, University Hospitals Gasthuisberg Leuven and KU Leuven, Leuven, Belgium. · Department of Oncology, Hôpital Riviera-Chablais, Vevey, Switzerland. · Department of Surgery, Technical University of Munich, Klinikum rechts der Isar, Munich, Germany. · Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden. · Nelune Cancer Centre, Prince of Wales Hospital, Prince of Wales Clinical School University of New South Wales, Randwick, NSW, Australia. · Department of Medical Oncology, University Hospital Basel, Basel, Switzerland. · Cancer Center, ASST Papa Giovanni XXIII, Bergamo, Italy. · Department of Gastroenterology, Gastrointestinal Cancer Unit, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium. · Vall d'Hebron University Hospital (HUVH), Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. · Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK. · Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan. · Gastrointestinal Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY, USA. · Department of Hematology, Oncology and Tumor Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany; Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany; Berlin Institute of Health, Berlin, Germany. · Department of Oncology, Karmanos Cancer Center, Wayne State University, Detroit, MI, USA. · Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy. · Department of Internal Medicine I, Medical University Vienna, Vienna, Austria. · Division of Solid Tumor Translational Oncology, West German Cancer Cancer, University Hospital Essen, Essen, Germany; German Cancer Consortium (DKTK, partner site Essen) and German Cancer Research Center, DKFZ, Heidelberg, Germany. · Department of Digestive Oncology, University Hospitals Leuven, Leuven, Belgium. · Department of Medical Oncology, Cancer Center Amsterdam, Academic Medical Center, Amsterdam, Netherlands. Electronic address: h.vanlaarhoven@amc.uva.nl. ·Lancet Oncol · Pubmed #29508762.

ABSTRACT: Variations in the reporting of potentially confounding variables in studies investigating systemic treatments for unresectable pancreatic cancer pose challenges in drawing accurate comparisons between findings. In this Review, we establish the first international consensus on mandatory baseline and prognostic characteristics in future trials for the treatment of unresectable pancreatic cancer. We did a systematic literature search to find phase 3 trials investigating first-line systemic treatment for locally advanced or metastatic pancreatic cancer to identify baseline characteristics and prognostic variables. We created a structured overview showing the reporting frequencies of baseline characteristics and the prognostic relevance of identified variables. We used a modified Delphi panel of two rounds involving an international panel of 23 leading medical oncologists in the field of pancreatic cancer to develop a consensus on the various variables identified. In total, 39 randomised controlled trials that had data on 15 863 patients were included, of which 32 baseline characteristics and 26 prognostic characteristics were identified. After two consensus rounds, 23 baseline characteristics and 12 prognostic characteristics were designated as mandatory for future pancreatic cancer trials. The COnsensus statement on Mandatory Measurements in unresectable PAncreatic Cancer Trials (COMM-PACT) identifies a mandatory set of baseline and prognostic characteristics to allow adequate comparison of outcomes between pancreatic cancer studies.

2 Clinical Trial nab-Paclitaxel plus gemcitabine for metastatic pancreatic cancer: long-term survival from a phase III trial. 2015

Goldstein, David / El-Maraghi, Robert Hassan / Hammel, Pascal / Heinemann, Volker / Kunzmann, Volker / Sastre, Javier / Scheithauer, Werner / Siena, Salvatore / Tabernero, Josep / Teixeira, Luis / Tortora, Giampaolo / Van Laethem, Jean-Luc / Young, Rosemary / Penenberg, Darryl Neil / Lu, Brian / Romano, Alfredo / Von Hoff, Daniel D. ·Prince of Wales Hospital, University of New South Wales, Sydney, NSW, Australia (DG) · Royal Victoria Regional Health Centre, Barrie, ON, Canada (RHEM) · Hôpital Beaujon, Clichy, France (PH) · Klinikum Grosshadern, University of Munich, Munich, Germany (VH) · Universitätsklinikum Würzburg, Würzburg, Germany (VK) · Hospital Clinico San Carlos, Madrid, Spain (JS) · Medizinische Universität Wien, Wien, Austria (WS) · Ospedale Niguarda Ca' Granda, Milan, Italy (SS) · Vall d'Hebron University Hospital and Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Barcelona, Spain (JT) · Hôpital Saint Antoine, Paris, France (LT) · Azienda Ospedaliera Universitaria Integrata and University of Verona, Verona, Italy (GT) · Hôpital Erasme, Brussels, Belgium (JLVL) · Royal Hobart Hospital, Hobart, Australia (RY) · Celgene Corporation, Summit, NJ (DNP) · Celgene Corporation, Summit, NJ (BL) · Celgene Corporation, Boudry, Switzerland (AR) · Virginia G. Piper Cancer Center at Scottsdale Healthcare/TGen, Scottsdale, AZ (DDVH). ·J Natl Cancer Inst · Pubmed #25638248.

ABSTRACT: BACKGROUND: Positive findings from the phase III MPACT trial led to the regulatory approval of nab-paclitaxel plus gemcitabine as a treatment option for patients with metastatic pancreatic cancer. This report is an update of overall survival (OS) based on longer follow-up. METHODS: Patients (n = 861) with metastatic pancreatic cancer and a Karnofsky performance status of 70 or greater were randomly assigned one to one to receive nab-paclitaxel + gemcitabine or gemcitabine alone. Efficacy data for this post hoc analysis were collected through May 9, 2013. Exploratory analyses of carbohydrate antigen 19-9 (CA19-9) and neutrophil-to-lymphocyte ratio (NLR) were conducted. The primary efficacy endpoint was OS, which was analyzed for all randomly assigned patients by the Kaplan-Meier method. All statistical tests were two-sided. RESULTS: The median OS was statistically significantly longer for nab-paclitaxel plus gemcitabine vs gemcitabine alone (8.7 vs 6.6 months, hazard ratio [HR] = 0.72, 95% confidence interval [CI] = 0.62 to 0.83, P < .001). Long-term (>three-year) survivors were identified in the nab-paclitaxel plus gemcitabine arm only (4%). In pooled treatment arm analyses, higher CA19-9 level and NLR at baseline were statistically significantly associated with worse OS. There appeared to be a treatment effect for OS favoring nab-paclitaxel plus gemcitabine over gemcitabine alone in poor-prognosis subgroups defined by these factors (HR = 0.612, P < .001 for CA19-9 level ≥ median and HR = 0.81, P = .079 for NLR > 5). CONCLUSIONS: These data confirm and extend the primary report of OS, supporting the superior efficacy of nab-paclitaxel plus gemcitabine over gemcitabine alone. Subgroup analyses support the relevance of CA 19-9 and NLR as prognostic markers in metastatic pancreatic cancer.

3 Clinical Trial Prognostic factors of survival in a randomized phase III trial (MPACT) of weekly nab-paclitaxel plus gemcitabine versus gemcitabine alone in patients with metastatic pancreatic cancer. 2015

Tabernero, Josep / Chiorean, E Gabriela / Infante, Jeffrey R / Hingorani, Sunil R / Ganju, Vinod / Weekes, Colin / Scheithauer, Werner / Ramanathan, Ramesh K / Goldstein, David / Penenberg, Darryl N / Romano, Alfredo / Ferrara, Stefano / Von Hoff, Daniel D. ·Medical Oncology Department, Vall d'Hebron University Hospital and Institute of Oncology, Universitat Autònoma de Barcelona, Barcelona, Spain; Division of Oncology, University of Washington, Seattle, Washington, USA; Department of Oncology/Hematology, Sarah Cannon Research Institute, Nashville, Tennessee, USA; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA; Department of Oncology, Peninsula Oncology Centre, Monash University, Frankston, Victoria, Australia; Division of Medical Oncology, University of Colorado Cancer Center, Aurora, Colorado, USA; Division of Clinical Oncology, Medizinische Universität Wien, Vienna, Austria; Mayo Clinic, Scottsdale, Arizona, USA; Department of Oncology, Prince of Wales Hospital, Randwick, New South Wales, Sydney, Australia; Celgene Corporation, Summit, New Jersey, USA; Department of Oncology, Virginia G. Piper Cancer Center at Scottsdale Healthcare/TGen, Scottsdale, Arizona, USA jtabernero@vhio.net. · Medical Oncology Department, Vall d'Hebron University Hospital and Institute of Oncology, Universitat Autònoma de Barcelona, Barcelona, Spain; Division of Oncology, University of Washington, Seattle, Washington, USA; Department of Oncology/Hematology, Sarah Cannon Research Institute, Nashville, Tennessee, USA; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA; Department of Oncology, Peninsula Oncology Centre, Monash University, Frankston, Victoria, Australia; Division of Medical Oncology, University of Colorado Cancer Center, Aurora, Colorado, USA; Division of Clinical Oncology, Medizinische Universität Wien, Vienna, Austria; Mayo Clinic, Scottsdale, Arizona, USA; Department of Oncology, Prince of Wales Hospital, Randwick, New South Wales, Sydney, Australia; Celgene Corporation, Summit, New Jersey, USA; Department of Oncology, Virginia G. Piper Cancer Center at Scottsdale Healthcare/TGen, Scottsdale, Arizona, USA. ·Oncologist · Pubmed #25582141.

ABSTRACT: BACKGROUND: nab-Paclitaxel in combination with gemcitabine has emerged as a new treatment option for patients with metastatic pancreatic cancer (MPC), based on superiority over gemcitabine demonstrated in the phase III MPACT trial. Previously, Karnofsky performance status (KPS) score and the presence of liver metastases were shown to be predictive of survival with nab-paclitaxel plus gemcitabine treatment. This analysis sought to further explore the relationship between clinical characteristics and survival in the MPACT trial and to identify potential predictors of overall survival and progression-free survival in patients with MPC. MATERIALS AND METHODS: Cox regression models adjusted for stratification factors and a stepwise multivariate analysis of prespecified baseline prognostic factors were performed. RESULTS: Treatment effect was significantly associated with survival, with a similar magnitude of reduction in risk of death compared with the previously reported primary analysis. Treatment effect consistently favored nab-paclitaxel plus gemcitabine across the majority of the prespecified factors. In addition to KPS score and presence of liver metastases, age and number of metastatic sites were independent prognostic factors of overall and progression-free survival. Baseline carbohydrate antigen 19-9 was not found to be an independent prognostic factor of survival in this analysis. CONCLUSION: The results of this analysis confirm broad utility of nab-paclitaxel plus gemcitabine for the treatment of MPC. In addition, these findings suggest that KPS score, presence of liver metastases, age, and number of metastatic sites are important predictors of survival that may be useful when making treatment decisions and designing future clinical trials.

4 Clinical Trial Clinical benefit response in pancreatic cancer trials revisited. 2014

Bernhard, Jürg / Dietrich, Daniel / Glimelius, Bengt / Bodoky, György / Scheithauer, Werner / Herrmann, Richard. ·SAKK Coordinating Center, Bern, Switzerland. ·Oncol Res Treat · Pubmed #24613908.

ABSTRACT: OBJECTIVES: Clinical benefit response (CBR), based on changes in pain, Karnofsky performance status, and weight, is an established palliative endpoint in trials for advanced gastrointestinal cancer. We investigated whether CBR is associated with survival, and whether CBR reflects a wide-enough range of domains to adequately capture patients' perception. METHODS: CBR was prospectively evaluated in an international phase III chemotherapy trial in patients with advanced pancreatic cancer (n = 311) in parallel with patient-reported outcomes (PROs). RESULTS: The median time to treatment failure was 3.4 months (range: 0-6). The majority of the CBRs (n = 39) were noted in patients who received chemotherapy for at least 5 months. Patients with CBR (n = 62) had longer survival than non-responders (n = 182) (hazard ratio = 0.69; 95% confidence interval: 0.51-0.94; p = 0.013). CBR was predicted with a sensitivity and specificity of 77-80% by various combinations of 3 mainly physical PROs. A comparison between the duration of CBR (n = 62, median = 8 months, range = 4-31) and clinically meaningful improvements in the PROs (n = 100-116; medians = 9-11 months, range = 4-24) showed similar intervals. CONCLUSION: CBR is associated with survival and mainly reflects physical domains. Within phase III chemotherapy trials for advanced gastrointestinal cancer, CBR can be replaced by a PRO evaluation, without losing substantial information but gaining complementary information.

5 Clinical Trial Phase III randomized comparison of gemcitabine versus gemcitabine plus capecitabine in patients with advanced pancreatic cancer. 2009

Cunningham, David / Chau, Ian / Stocken, Deborah D / Valle, Juan W / Smith, David / Steward, William / Harper, Peter G / Dunn, Janet / Tudur-Smith, Catrin / West, Julia / Falk, Stephen / Crellin, Adrian / Adab, Fawzi / Thompson, Joyce / Leonard, Pauline / Ostrowski, Joe / Eatock, Martin / Scheithauer, Werner / Herrmann, Richard / Neoptolemos, John P. ·Royal Marsden National HealthService (NHS) Foundation Trust, London and Surrey, United Kingdom. david.cunningham@rmh.nhs.uk ·J Clin Oncol · Pubmed #19858379.

ABSTRACT: PURPOSE: Both gemcitabine (GEM) and fluoropyrimidines are valuable treatment for advanced pancreatic cancer. This open-label study was designed to compare the overall survival (OS) of patients randomly assigned to GEM alone or GEM plus capecitabine (GEM-CAP). PATIENTS AND METHODS: Patients with previously untreated histologically or cytologically proven locally advanced or metastatic carcinoma of the pancreas with a performance status On the basis of our trial and the meta-analysis, GEM-CAP should be considered as one of the standard first-line options in locally advanced and metastatic pancreatic cancer.

6 Clinical Trial Phase III trial of bevacizumab in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer. 2009

Van Cutsem, Eric / Vervenne, Walter L / Bennouna, Jaafar / Humblet, Yves / Gill, Sharlene / Van Laethem, Jean-Luc / Verslype, Chris / Scheithauer, Werner / Shang, Aijing / Cosaert, Jan / Moore, Malcolm J. ·University Hospital Gasthuisberg/Leuven, Digestive Oncology Unit, Herestraat 49, B-3000 Leuven, Belgium. eric.vancutsem@uz.kuleuven.ac.be ·J Clin Oncol · Pubmed #19307500.

ABSTRACT: PURPOSE: Treatment with gemcitabine provides modest benefits in patients with metastatic pancreatic cancer. The addition of erlotinib to gemcitabine shows a small but significant improvement in overall survival (OS) versus gemcitabine alone. Phase II results for bevacizumab plus gemcitabine provided the rationale for a phase III trial of gemcitabine-erlotinib plus bevacizumab or placebo. PATIENTS AND METHODS: Patients with metastatic pancreatic adenocarcinoma were randomly assigned to receive gemcitabine (1,000 mg/m(2)/week), erlotinib (100 mg/day), and bevacizumab (5 mg/kg every 2 weeks) or gemcitabine, erlotinib, and placebo in this double-blind, phase III trial. Primary end point was OS; secondary end points included progression-free survival (PFS), disease control rate, and safety. RESULTS: A total of 301 patients were randomly assigned to the placebo group and 306 to the bevacizumab group. Median OS was 7.1 and 6.0 months in the bevacizumab and placebo arms, respectively (hazard ratio [HR], 0.89; 95% CI, 0.74 to 1.07; P = .2087); this difference was not statistically significant. Adding bevacizumab to gemcitabine-erlotinib significantly improved PFS (HR, 0.73; 95% CI, 0.61 to 0.86; P = .0002). Treatment with bevacizumab plus gemcitabine-erlotinib was well tolerated: safety data did not differ from previously described safety profiles for individual drugs. CONCLUSION: The primary objective was not met. The addition of bevacizumab to gemcitabine-erlotinib did not lead to a statistically significant improvement in OS in patients with metastatic pancreatic cancer. PFS, however, was significantly longer in the bevacizumab group compared with placebo. No unexpected safety events were observed from adding bevacizumab to gemcitabine-erlotinib.

7 Clinical Trial Clinical benefit and quality of life in patients with advanced pancreatic cancer receiving gemcitabine plus capecitabine versus gemcitabine alone: a randomized multicenter phase III clinical trial--SAKK 44/00-CECOG/PAN.1.3.001. 2008

Bernhard, Jürg / Dietrich, Daniel / Scheithauer, Werner / Gerber, Daniela / Bodoky, György / Ruhstaller, Thomas / Glimelius, Bengt / Bajetta, Emilio / Schüller, Johannes / Saletti, Piercarlo / Bauer, Jean / Figer, Arie / Pestalozzi, Bernhard C / Köhne, Claus-Henning / Mingrone, Walter / Stemmer, Salomon M / Tàmas, Karin / Kornek, Gabriela V / Koeberle, Dieter / Herrmann, Richard / Anonymous7470604. ·Swiss Group for Clinical Cancer Research Coordinating Center, Bern, Switzerland. juerg.bernhard@ibcsg.org ·J Clin Oncol · Pubmed #18669454.

ABSTRACT: PURPOSE: To compare clinical benefit response (CBR) and quality of life (QOL) in patients receiving gemcitabine (Gem) plus capecitabine (Cap) versus single-agent Gem for advanced/metastatic pancreatic cancer. PATIENTS AND METHODS: Patients were randomly assigned to receive GemCap (oral Cap 650 mg/m(2) twice daily on days 1 through 14 plus Gem 1,000 mg/m(2) in a 30-minute infusion on days 1 and 8 every 3 weeks) or Gem (1,000 mg/m(2) in a 30-minute infusion weekly for 7 weeks, followed by a 1-week break, and then weekly for 3 weeks every 4 weeks) for 24 weeks or until progression. CBR criteria and QOL indicators were assessed over this period. CBR was defined as improvement from baseline for >or= 4 consecutive weeks in pain (pain intensity or analgesic consumption) and Karnofsky performance status, stability in one but improvement in the other, or stability in pain and performance status but improvement in weight. RESULTS: Of 319 patients, 19% treated with GemCap and 20% treated with Gem experienced a CBR, with a median duration of 9.5 and 6.5 weeks, respectively (P < .02); 54% of patients treated with GemCap and 60% treated with Gem had no CBR (remaining patients were not assessable). There was no treatment difference in QOL (n = 311). QOL indicators were improving under chemotherapy (P < .05). These changes differed by the time to failure, with a worsening 1 to 2 months before treatment failure (all P < .05). CONCLUSION: There is no indication of a difference in CBR or QOL between GemCap and Gem. Regardless of their initial condition, some patients experience an improvement in QOL on chemotherapy, followed by a worsening before treatment failure.

8 Article Biochemical and genetic predictors of overall survival in patients with metastatic pancreatic cancer treated with capecitabine and nab-paclitaxel. 2017

Bianconi, Daniela / Heller, Gerwin / Spies, Daniel / Herac, Merima / Gleiss, Andreas / Liebmann-Reindl, Sandra / Unseld, Matthias / Kieler, Markus / Scheithauer, Werner / Streubel, Berthold / Zielinski, Christoph C / Prager, Gerald W. ·Department of Medicine I, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria. · Swiss Federal Institute of Technology Zurich, Department of Biology, Institute of Molecular Health Sciences, Otto-Stern Weg 7, 8093, Zurich, Switzerland. · Life Science Zurich Graduate School, Molecular Life Science Program, Institute of Molecular Life Science, University of Zurich, Winterthurerstrasse 190, Zurich, 8057, Switzerland, Austria. · Clinical Institute of Pathology, Medical University of Vienna, Vienna, Austria. · Center for Medical Statistics, Informatics, and Intelligent Systems, Medical University of Vienna, Vienna, Austria. · Core facilities, Medical University of Vienna, Vienna, Austria. · Department of Medicine I, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria. gerald.prager@meduniwien.ac.at. ·Sci Rep · Pubmed #28687745.

ABSTRACT: Pancreatic cancer is a dismal disease with a mortality rate almost similar to its incidence rate. To date, there are neither validated predictive nor prognostic biomarkers for this lethal disease. Thus, the aim of the present study was to retrospectively investigate the capability of biochemical parameters and molecular profiles to predict survival of patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) who participated in a phase II clinical trial to test the safety and efficacy of the combination treatment of capecitabine plus nab-paclitaxel. Herein, we investigated the association of 18 biochemical parameters obtained from routine diagnosis and the clinical outcome of the 30 patients enrolled in the clinical trial. Furthermore, we analysed formalin-fixed paraffin-embedded (FFPE) tumour tissue to identify molecular biomarkers via RNA seq and the Illumina TruSeq Amplicon Cancer panel which covers 48 hotspot genes. Our analysis identified SERPINB7 as a novel transcript and a DNA mutation signature that might predict a poor outcome of disease. Moreover, we identified the bilirubin basal level as an independent predictive factor for overall survival in our study cohort.

9 Article Response to GEMOX plus erlotinib in pancreatic cancer is associated with ERCC1 overexpression. 2014

Fuereder, Thorsten / Stift, Judith / Kuehrer, Irene / Stranzl, Nadja / Hoeflmayer, Doris / Kornek, Gabriela / Scheithauer, Werner. ·Department of Internal Medicine I & CCC, Medical University of Vienna, Vienna, Austria. ·Eur J Clin Invest · Pubmed #25145842.

ABSTRACT: INTRODUCTION: There are no data about the efficacy of gemcitabine in combination with oxaliplatin (GEMOX) and erlotinib for the treatment of metastatic pancreatic cancer (mPC). Thus, we performed this retrospective analysis in mPC patients to investigate the activity and safety of GEMOX plus erlotinib and correlated the benefit with ERCC1 expression, a potential biomarker for treatment response. PATIENTS AND METHODS: Patients with untreated mPC receiving off-protocol GEMOX plus erlotinib were included. Data collection included baseline demographic, response and toxicity data as well as PFS and OS. Additionally, immunohistochemistry was performed to stain for ERCC1 expression. RESULTS: A total of 51 patients were included. The median age was 62 years and the median ECOG performance score was 1 (range, 0-1). Objective response or disease stabilization was achieved in 54% of the patients. The median PFS was 4·4 months (95% CI 4·4-5·4) and median OS was 8·5 months (95% CI 6·1-10·9). The 27 patients, who benefited from this regimen, had a median PFS of 6·7, a median OS of 11·2 months and an overexpression of ERCC1 (histoscore 10, P ≤ 0·05) compared to nonresponders (histoscore 7·2). Myelosuppression was the most frequent side effect. The most common severe nonhematological toxicities were diarrhoea and skin toxicity in six (12%) patients each. CONCLUSIONS: These data suggest that the combination of GEMOX plus erlotinib is safe and active in about half of the patients. Patients, who had a higher ERCC1 staining pattern, benefited most from this therapy. Prospective biomarker studies are warranted to confirm these findings.

10 Article Microparticle-associated tissue factor activity in patients with pancreatic cancer: correlation with clinicopathological features. 2013

Thaler, Johannes / Ay, Cihan / Mackman, Nigel / Metz-Schimmerl, Sylvia / Stift, Judith / Kaider, Alexandra / Müllauer, Leonhard / Gnant, Michael / Scheithauer, Werner / Pabinger, Ingrid. ·Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria. ·Eur J Clin Invest · Pubmed #23398637.

ABSTRACT: BACKGROUND: Patients with pancreatic cancer have an unfavourable prognosis. A central role in pancreatic cancer progression has been suggested for tissue factor (TF), the main initiator of the blood coagulation cascade. We hypothesized that elevated levels of plasma microparticle (MP)-associated TF activity might indicate the presence of poorly differentiated pancreatic cancer, disease dissemination and infiltration of peripancreatic vessels. METHODS: MP-TF activity was measured in 73 pancreatic cancer patients and 22 healthy controls. Abdominal computerized tomography (CT) scans performed at study inclusion were investigated for probability of tumoural vascular invasion. In addition, intratumoural TF expression, D-dimer and CA 19-9 levels were determined. RESULTS: MP-TF activity (pg/mL) was significantly higher in patients (median: 0·37 [range: 0·00-11·91]) than in controls (median: 0·05 [range: 0·00-0·76]; P < 0·001). When pancreatic cancer patients were compared with regard to stage and grade, significantly elevated levels of MP-TF activity were only present in those with poorly differentiated metastatic nonresectable tumours (n = 11, median: 2·95 [range: 0·25-11·91]). In three patients with poorly differentiated tumours, a high probability of vascular invasion was found (MP-TF activity in these cases: 2·95, 7·00 and 10·34). MP-TF activity correlated strongly with CA 19-9 (r = 0·60) and weakly with D-dimer (r = 0·33) levels. Immunohistochemical staining for TF was positive in 14 of 15 resected tumours. MP-TF activity was associated with an increased risk of mortality (HR: 1·8 per doubling in MP-TF activity, [95% CI: 1·4-2·4, P < 0·001]). CONCLUSION: MP-TF activity might represent a biomarker for a poorly differentiated and invasive pancreatic cancer phenotype and poor survival.

11 Article Estimating prognosis and palliation based on tumour marker CA 19-9 and quality of life indicators in patients with advanced pancreatic cancer receiving chemotherapy. 2010

Bernhard, J / Dietrich, D / Glimelius, B / Hess, V / Bodoky, G / Scheithauer, W / Herrmann, R. ·SAKK Coordinating Center, Bern, Switzerland. juerg.bernhard@ibcsg.org ·Br J Cancer · Pubmed #20877359.

ABSTRACT: BACKGROUND: To investigate the prognostic value of quality of life (QOL) relative to tumour marker carbohydrate antigen (CA) 19-9, and the role of CA 19-9 in estimating palliation in patients with advanced pancreatic cancer receiving chemotherapy. METHODS: CA 19-9 serum concentration was measured at baseline and every 3 weeks in a phase III trial (SAKK 44/00-CECOG/PAN.1.3.001). Patients scored QOL indicators at baseline, and before each administration of chemotherapy (weekly or bi-weekly) for 24 weeks or until progression. Prognostic factors were investigated by Cox models, QOL during chemotherapy by mixed-effect models. RESULTS: Patient-rated pain (P<0.02) and tiredness (P<0.03) were independent predictors for survival, although less prognostic than CA 19-9 (P<0.001). Baseline CA 19-9 did not predict QOL during chemotherapy, except for a marginal effect on pain (P<0.05). Mean changes in physical domains across the whole observation period were marginally correlated with the maximum CA 19-9 decrease. Patients in a better health status reported the most improvement in QOL within 20 days before maximum CA 19-9 decrease. They indicated substantially less pain and better physical well-being, already, early on during chemotherapy with a maximum CA 19-9 decrease of ≥50% vs <50%. CONCLUSION: In advanced pancreatic cancer, pain and tiredness are independent prognostic factors for survival, although less prognostic than CA 19-9. Quality of life improves before best CA 19-9 response but the maximum CA 19-9 decrease has no impact on subsequent QOL. To estimate palliation by chemotherapy, patient's perception needs to be taken into account.

12 Article Limited value of CA 19-9 in predicting early treatment failure in patients with advanced pancreatic cancer. 2009

Vormittag, Laurenz / Gleiss, Andreas / Scheithauer, Werner / Lang, Fritz / Laengle, Friedrich / Kornek, Gabriela V. ·Division of Clinical Oncology, Department of Medicine I and Cancer Center, Medical University Vienna, Vienna, Austria. ·Oncology · Pubmed #19628952.

ABSTRACT: OBJECTIVE: The role of CA 19-9 in monitoring treatment response in advanced pancreatic cancer remains uncertain. We assessed its value in predicting early failure of first-line chemotherapy. METHODS: Data of 84 patients with advanced pancreatic cancer who had received first-line chemotherapy were analyzed with regard to changes in CA 19-9 during the first 2 months of treatment. RESULTS: Median time to progression and overall survival in patients with a transient increase in CA 19-9 during month 1 (n = 15; 5.5 and 13 months) and in those with no increase during the 2 months (n = 52; 6.5 and 12 months) were comparable and slightly above the median values of the entire study population. The hazard ratios for disease progression for a 20% increase in CA 19-9 during the first and second month of therapy were 1.065 and 1.339 in the univariate- and 1.092 and 1.298 in the multiple Cox regression model, respectively. CA 19-9 did not influence survival. CONCLUSION: Our results suggest that early CA 19-9 measurements are weakly associated with disease progression rather than survival in patients with advanced pancreatic cancer receiving palliative chemotherapy. In view of a possible tumor marker flare, values after the first month of therapy must be interpreted with caution.

13 Article CA 19-9 tumour-marker response to chemotherapy in patients with advanced pancreatic cancer enrolled in a randomised controlled trial. 2008

Hess, Viviane / Glimelius, Bengt / Grawe, Philipp / Dietrich, Daniel / Bodoky, György / Ruhstaller, Thomas / Bajetta, Emilio / Saletti, Piercarlo / Figer, Arie / Scheithauer, Werner / Herrmann, Richard. ·Division of Medical Oncology, Department of Internal Medicine, University Hospital Basel, Basel, Switzerland. vhess@uhbs.ch ·Lancet Oncol · Pubmed #18249033.

ABSTRACT: BACKGROUND: Several studies in patients undergoing chemotherapy for advanced pancreatic carcinoma have linked a decrease in the concentration of the tumour marker carbohydrate antigen (CA) 19-9 to lengthened survival. The aim of this study was to test the hypotheses that an early decrease in baseline serum CA 19-9 concentration (on day 42, after two cycles of chemotherapy) by at least 50% is associated with lengthened survival, and that a decrease in CA 19-9 concentration of at least 50% from the baseline concentration to the lowest value measured at any time during treatment (nadir) is of prognostic significance, enabling its use as a surrogate endpoint for survival. METHODS: CA 19-9 serum concentration was measured at baseline and every 3 weeks thereafter in patients with histologically proven advanced pancreatic carcinoma enrolled in a randomised trial of gemcitabine versus gemcitabine plus capecitabine. Patients were excluded if baseline serum CA 19-9 concentration was below the upper limit of normal (ULN) in the laboratory or if this measurement was missing. Comparisons of survival between patients with and without a CA 19-9 response were corrected for the guarantee-time bias by the landmark method. The trial on which this study is based is registered on the clinical trials site of the US National Cancer Institute website http://www.clinicaltrials.gov/ct/show/NCT00030732. FINDINGS: 247 of 319 randomised patients were assessable for analysis of baseline serum CA 19-9 concentration, and, of these, 175 patients were assessable for tumour-marker response to treatment. Median overall survival for patients with a baseline CA 19-9 concentration equal to or above the median value (ie, 59xULN) was 5.8 months (95% CI 5.1-7.0), which was significantly shorter than that for patients with baseline concentrations below the median value (10.3 months [95% CI 8.6-12.8], p<0.0001). An early decrease in CA 19-9 concentration of at least 50% after two cycles of chemotherapy was not associated with a longer overall survival compared with patients who did not have a decrease of at least 50% (median 10.1 months [9.2-12.7] vs 8.6 months [6.9-11.2], p=0.53; hazard ratio for death 1.11 [0.81-1.52]). Furthermore, a decrease in CA 19-9 concentration of at least 50% reached at the CA 19-9 nadir concentration was not associated with a longer overall survival compared with those patients who did not have a decrease of at least 50% (median 7.8 months [6.5.10.1] vs 6.7 months [5.5-9.8], p=0.74; 0.95 [0.69-1.31]) after adjusting for the guarantee-time bias. INTERPRETATION: Pretreatment serum CA 19-9 concentration is an independent prognostic factor for survival, but a decrease in concentration during chemotherapy is not significantly associated with lengthened survival compared with those who did not have a corresponding decrease. Our data suggest that CA 19-9 response during chemotherapy is not a valid surrogate endpoint for survival in clinical trials.