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Pancreatic Neoplasms: HELP
Articles by Jens T. Siveke
Based on 59 articles published since 2010
(Why 59 articles?)
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Between 2010 and 2020, J. Siveke wrote the following 59 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3
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 Guideline [S3-guideline exocrine pancreatic cancer]. 2013

Seufferlein, T / Porzner, M / Becker, T / Budach, V / Ceyhan, G / Esposito, I / Fietkau, R / Follmann, M / Friess, H / Galle, P / Geissler, M / Glanemann, M / Gress, T / Heinemann, V / Hohenberger, W / Hopt, U / Izbicki, J / Klar, E / Kleeff, J / Kopp, I / Kullmann, F / Langer, T / Langrehr, J / Lerch, M / Löhr, M / Lüttges, J / Lutz, M / Mayerle, J / Michl, P / Möller, P / Molls, M / Münter, M / Nothacker, M / Oettle, H / Post, S / Reinacher-Schick, A / Röcken, C / Roeb, E / Saeger, H / Schmid, R / Schmiegel, W / Schoenberg, M / Siveke, J / Stuschke, M / Tannapfel, A / Uhl, W / Unverzagt, S / van Oorschot, B / Vashist, Y / Werner, J / Yekebas, E / Anonymous260779 / Anonymous270779 / Anonymous280779. ·Klinik für Innere Medizin I, Universitätsklinikum Ulm. · Klinik für Allgemeine Chirurgie, Viszeral-, Thorax-, Transplantations- und Kinderchirurgie, Universitätsklinikum Kiel. · Klinik für Radioonkologie und Strahlentherapie, Charité Universitätsmedizin Berlin. · Chirurgische Klinik und Poliklinik, Klinikum rechts der Isar, TU München. · Institut für Allgemeine Pathologie, Klinikum rechts der Isar, TU München. · Strahlenklinik, Universitätsklinikum Erlangen. · Leitlinienprogramm Onkologie, Deutsche Krebsgesellschaft e. V., Berlin. · I. Medizinische Klinik und Poliklinik, Universitätsmedizin Mainz. · Klinik für Allgemeine Innere Medizin, Onkologie/Hämatologie, Gastroenterologie und Infektiologie, Klinikum Esslingen. · Klinik für Allgemeine Chirurgie, Viszeral-, Gefäß- und Kinderchirurgie, Universitätsklinikum des Saarlandes Homburg/Saar. · Klinik für Gastroenterologie, Endokrinologie und Stoffwechsel, Universitätsklinikum Gießen und Marburg. · Medizinischen Klinik und Poliklinik III, Klinikum der Universität München LMU. · Chirurgische Klinik, Universitätsklinikum Erlangen. · Klinik für Allgemein- und Viszeralchirurgie, Universitätsklinikum Freiburg. · Klinik für Allgemein-, Viszeral- und Thoraxchirurgie, Universitätsklinikum Hamburg-Eppendorf. · Klinik für Allgemeine Chirurgie, Thorax-, Gefäß- und Transplantationschirurgie, Universitätsmedizin Rostock. · AWMF-Institut für Medizinisches Wissensmanagement, Marburg. · Medizinische Klinik I, Klinikum Weiden. · Klinik für Allgemein-, Gefäß- und Viszeralchirurgie, Martin-Luther-Krankenhaus Berlin. · Klinik und Poliklinik für Innere Medizin A, Universitätsmedizin Greifswald. · Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm. · Institut für Pathologie, Marienkrankenhaus Hamburg. · Medizinische Klinik - Schwerpunkt Gastroenterologie, Endokrinologie, Infektiologie, Caritasklinikum Saarbrücken. · Institut für Pathologie, Universitätsklinikum Ulm. · Klinik und Poliklinik für Strahlentherapie und Radiologische Onkologie, Klinikum rechts der Isar, TU München. · Klinik für Strahlentherapie und Radioonkologie, Klinikum Stuttgart. · AWMF-Institut für Medizinisches Wissensmanagement, Berlin. · Medizinische Klinik mit Schwerpunkt Hämatologie und Onkologie, Charité Universitätsmedizin Berlin. · Chirurgische Klinik, Universitätsmedizin Mannheim. · Abt. für Hämatologie und Onkologie, St. Josef-Hospital, Klinikum der Ruhr-Universität Bochum. · Institut für Pathologie, Universitätsklinikum Kiel. · Medizinische Klinik II, SP Gastroenterologie, Universitätsklinikum Gießen und Marburg. · Klinik für Viszeral-, Thorax- und Gefäßchirurgie, Universitätsklinikum Dresden. · II. Medizinische Klinik und Poliklinik, Klinikum rechts der Isar, TU München. · Medizinische Klinik, Klinikum der Ruhr-Universität Bochum. · Klinik für Chirurgie, Rotkreuzklinikum München. · Klinik für Strahlentherapie, Universitätsklinikum Essen. · Institut für Pathologie, Ruhr-Universität Bochum. · Chirurgische Klinik, St. Josef-Hospital, Klinikum der Ruhr-Universität Bochum. · Institut für Medizinische Epidemiologie, Biometrie und Informatik, Martin-Luther-Universität Halle-Wittenberg. · Klinik und Poliklinik für Strahlentherapie, Universitätsklinikum Würzburg. · Klinik für Allgemeine, Viszerale und Transplantationschirurgie, Universitätsklinikum Heidelberg. · Klinik für Allgemein-, Thorax- und Viszeralchirurgie, Klinikum Darmstadt. ·Z Gastroenterol · Pubmed #24338757.

ABSTRACT: -- No abstract --

3 Editorial The increasing diversity of KRAS signaling in pancreatic cancer. 2014

Siveke, Jens T. ·II. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany. Electronic address: jens.siveke@lrz.tum.de. ·Gastroenterology · Pubmed #25167989.

ABSTRACT: -- No abstract --

4 Editorial KRAS above and beyond - EGFR in pancreatic cancer. 2012

Siveke, Jens T / Crawford, Howard C. · ·Oncotarget · Pubmed #23174662.

ABSTRACT: -- No abstract --

5 Review Immunotherapy and Combination Strategies in Pancreatic Cancer: Current Status and Emerging Trends. 2018

Cheung, Phyllis F / Lutz, Manfred / Siveke, Jens T. · ·Oncol Res Treat · Pubmed #29705789.

ABSTRACT: Pancreatic cancer is among the most aggressive malignancies with no effective therapeutic options thus far. Immunotherapy has recently emerged as a promising alternative for the treatment of various solid tumors. In particular, promising results in clinical trials were observed for therapies targeting immune checkpoint molecules. Efforts have been put into investigating the potential of immunotherapy in treating pancreatic cancer. While most of the clinical trial results are still being awaited, several intrinsic features of pancreatic cancer such as low mutational load and the presence of highly immunosuppressive desmoplasia significantly hamper the efficacy of immunotherapy in this disease. These unique features of pancreatic cancer, however, have advanced our understanding of tumor immunology and might help to tailor the future direction of immunotherapy. In this review, we summarize the current immunotherapeutic strategies and clinical trials targeting checkpoint molecules in pancreatic cancer. Emerging trends towards various combinations with therapies targeting immunosuppressive myeloid cells are also discussed.

6 Review Epigenetic treatment of pancreatic cancer: is there a therapeutic perspective on the horizon? 2017

Hessmann, Elisabeth / Johnsen, Steven A / Siveke, Jens T / Ellenrieder, Volker. ·Department of Gastroenterology and Gastrointestinal Oncology, University Medical Center Goettingen, Goettingen, Germany. · Department of General, Visceral and Pediatric Surgery, University Medical Center Goettingen, Goettingen, Germany. · Division of Solid Tumor Translational Oncology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany. · West German Cancer Center, University Hospital Essen, Essen, Germany. ·Gut · Pubmed #27811314.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) constitutes one of the most aggressive malignancies with a 5-year survival rate of <7%. Due to growing incidence, late diagnosis and insufficient treatment options, PDAC is predicted to soon become one of the leading causes of cancer-related death. Although intensified cytostatic combinations, particularly gemcitabine plus nab-paclitaxel and the folinic acid, fluorouracil, irinotecan, oxaliplatin (FOLFIRINOX) protocol, provide some improvement in efficacy and survival compared with gemcitabine alone, a breakthrough in the treatment of metastatic pancreatic cancer remains out of sight. Nevertheless, recent translational research activities propose that either modulation of the immune response or pharmacological targeting of epigenetic modifications alone, or in combination with chemotherapy, might open highly powerful therapeutic avenues in GI cancer entities, including pancreatic cancer. Deregulation of key epigenetic factors and chromatin-modifying proteins, particularly those responsible for the addition, removal or recognition of post-translational histone modifications, are frequently found in human pancreatic cancer and hence constitute particularly exciting treatment opportunities. This review summarises both current clinical trial activities and discovery programmes initiated throughout the biopharma landscape, and critically discusses the chances, hurdles and limitations of epigenetic-based therapy in future PDAC treatment.

7 Review MYC in pancreatic cancer: novel mechanistic insights and their translation into therapeutic strategies. 2016

Hessmann, E / Schneider, G / Ellenrieder, V / Siveke, J T. ·Clinic for Gastroenterology and Gastrointestinal Oncology, University Medical Center Goettingen, Goettingen, Germany. · Department of Internal Medicine II, Medizinische Klinik, Klinikum rechts der Isar, Technische Universität, Munich, Germany. · German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany. ·Oncogene · Pubmed #26119937.

ABSTRACT: Owing to its aggressiveness, late detection and marginal therapeutic accessibility, pancreatic ductal adenocarcinoma (PDAC) remains a most challenging malignant disease. Despite scientific progress in the understanding of the mechanisms that underly PDAC initiation and progression, the successful translation of experimental findings into effective new therapeutic strategies remains a largely unmet need. The oncogene MYC is activated in many PDAC cases and is a master regulator of vital cellular processes. Excellent recent studies have shed new light on the tremendous functions of MYC in cancer and identified inhibition of MYC as a likewise beneficial and demanding effort. This review will focus on mechanisms that contribute to deregulation of MYC expression in pancreatic carcinogenesis and progression and will summarize novel biological findings from recent in vivo models. Finally, we provide a perspective, how regulation of MYC in PDAC may contribute to the development of new therapeutic approaches.

8 Review Patients with Advanced Pancreatic Cancer and Hyperbilirubinaemia: Review and German Expert Opinion on Treatment with nab-Paclitaxel plus Gemcitabine. 2015

Vogel, Arndt / Kullmann, Frank / Kunzmann, Volker / Al-Batran, Salah-Eddin / Oettle, Helmut / Plentz, Ruben / Siveke, Jens / Springfeld, Christoph / Riess, Hanno. ·Klinik fx00FC;r Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover, Germany. ·Oncol Res Treat · Pubmed #26599274.

ABSTRACT: In patients with advanced unresectable pancreatic cancer, the prognosis is generally poor. Within recent years, new treatment options such as the FOLFIRINOX regimen (5-fluorouracil, leucovorin, irinotecan and oxaliplatin) or the combination of nanoparticle albumin-bound (nab)-paclitaxel plus gemcitabine have shown a clinically relevant survival benefit over the standard gemcitabine in patients with good performance status. Unfortunately, patients with hyperbilirubinaemia, who constitute a substantial proportion of the pancreatic cancer patients, have been excluded from most clinical studies. Consequently, our knowledge on the appropriate medical treatment of this patient group is limited. In a meeting of German medical oncology experts, the available clinical evidence and own clinical experience regarding the management of patients with advanced pancreatic cancer and hyperbilirubinaemia was discussed. The present publication summarises the discussion outcomes with regard to appropriate management of these patients, including consensus-based recommendations for nab-paclitaxel/gemcitabine treatment, according to the best available evidence. In summary, knowledge of the underlying aetiology of hyperbilirubinaemia and the metabolisation routes of the cytotoxic drugs is crucial before initiating chemotherapy. As effective treatment options should also be made available to patients with comorbid conditions, including hyperbilirubinaemia, the experts provide advice for an initial dose reduction of chemotherapy with nab-paclitaxel/gemcitabine based on the total bilirubin level in patients with biliary obstruction or extensive liver metastasis.

9 Review Translational research in pancreatic ductal adenocarcinoma: current evidence and future concepts. 2014

Kruger, Stephan / Haas, Michael / Ormanns, Steffen / Bächmann, Sibylle / Siveke, Jens T / Kirchner, Thomas / Heinemann, Volker / Boeck, Stefan. ·Stephan Kruger, Michael Haas, Sibylle Bächmann, Volker Heinemann, Stefan Boeck, Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, D-81377 Munich, Germany. ·World J Gastroenterol · Pubmed #25152580.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDA) is one of the major causes for cancer death worldwide. Treatment of metastatic disease remains challenging as only certain patients benefit from advances made with the intensified chemotherapy regimen folinic acid, irinotecan and oxaliplatin, the epidermal growth factor receptor inhibitor erlotinib or the recently FDA-approved nab-paclitaxel. Up to date, no established approach for prediction of treatment response or specific treatment allocation exists. Translational research was able to identify a number of potential biomarkers that might help to improve the dismal prognosis of PDA by facilitating upfront treatment allocation. This topic highlight is focused on current evidence on potential biomarkers for tumor biology, prognosis and prediction of treatment efficacy.

10 Review Approach to cystic lesions of the pancreas. 2014

Schmid, Roland M / Siveke, Jens T. ·II. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Ismaningerstr. 22, 81675, München, Deutschland, roland.schmid@lrz.tum.de. ·Wien Med Wochenschr · Pubmed #24254128.

ABSTRACT: Cystic lesions of the pancreas are detected more frequently due to the improvement of imaging technologies. Their prevalence increases with age. In 95 % of cases, the spectrum of cystic neoplasia includes intraductal papillary mucinous neoplasia (IPMN), mucinous cystic neoplasia (MCN), serous cystic neoplasia, and solid pseudopapillary neoplasia (SPN). Diagnostic procedures aim to distinguish between neoplastic cystic and non-neoplastic cystic lesions as well as serous and mucinous lesions because of their different malignant potential. In most cases,cystic lesions are detected incidentally by computed tomography and magnetic resonance imaging (MRI) performed for other reasons. In our opinion, MRI/magnetic resonance cholangiopancreatography (MRCP) and endoscopic ultrasound (EUS) are complementary diagnostic procedures. In doubtful cases, cyst fluid analysis might be performed. The most frequent lesions are IPMNs. MRI/MRCP allows the detection of the number of cystic lesions, the relation to the main pancreatic duct, and the size of the lesion. EUS is superior to evaluate mural nodules. The relation to the main pancreatic duct can more easily appreciated with secretin MRI, MCN, SPN as well as main-duct type IPMN and BD-IPMN with "high-risk stigmata" for malignancy should be resected. Asymptomatic BD-IPMN without mural nodules, no main duct involvement, and a size less than 30 mm can be followed with a watchful waiting strategy.

11 Review The role of insulin and IGF system in pancreatic cancer. 2013

Trajkovic-Arsic, Marija / Kalideris, Evdokia / Siveke, Jens T. ·II Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Ismaningerstr 22, 81675 Munich, Germany. trajkovicmarija1@gmail.com ·J Mol Endocrinol · Pubmed #23493758.

ABSTRACT: The importance of the IGF system in carcinogenesis has been established for many solid cancers. It is well known that individuals with higher circulating levels of the IGF1 ligand present an increased risk of cancer. However, therapies with monoclonal antibodies targeting the IGF1 receptor (IGF1R) have been largely unsuccessful. One of the potential reasons for this failure is the existence of the highly homologous insulin receptor (IR), which appears to be at least equally efficient as the IGF1R in the transition of mitogenic signals to the nucleus and promotion of cell growth. Furthermore, IGF1 and insulin receptors can form hybrid receptors sensitive to stimulation of all three ligands of the system: insulin, IGF1, and IGF2. Although the connection between insulin, diabetes, and cancer has been established for years now, clear evidence that demonstrate the redundancy of insulin and insulin receptors and insulin-like growth factors and their receptors in cancer is missing. In this review, we focus on the contribution of insulin and IGFs to carcinogenesis in the insulin-producing organ, the pancreas. We give a short summary on the complexity of insulin and the IGF system in the pancreas and their potential roles in pancreatic cancer, especially pancreatic ductal adenocarcinoma. Finally, we discuss drug-targeting options of this system and the rationale of simultaneous targeting of both the insulin and the IGF systems.

12 Review Genetically engineered mouse models of pancreatic cancer: unravelling tumour biology and progressing translational oncology. 2012

Mazur, Pawel K / Siveke, Jens T. ·II. Medizinische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Ismaningerstr. 22, München 81675, Germany. ·Gut · Pubmed #21873467.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) remains a devastating disease despite tremendous scientific efforts. Numerous trials have failed to improve the outcome on this deadliest of all major cancers. Potential causes include a still insufficient understanding of key features of this cancer and imperfect preclinical models for identification of active agents and mechanisms of therapeutic responses and resistance. Modern genetically engineered mouse models of PDAC faithfully recapitulate the genetic and biological evolution of human PDAC, thereby providing a potentially powerful tool for addressing tumour biological issues as well as strategies for early detection and assessment of responses to therapeutic interventions. Here, the authors will discuss opportunities and challenges in the application of genetically engineered mouse models for translational approaches in pancreatic cancer and provide a non-exhaustive list of examples with already existing or future clinical relevance.

13 Clinical Trial Survival with nal-IRI (liposomal irinotecan) plus 5-fluorouracil and leucovorin versus 5-fluorouracil and leucovorin in per-protocol and non-per-protocol populations of NAPOLI-1: Expanded analysis of a global phase 3 trial. 2018

Chen, Li-Tzong / Siveke, Jens T / Wang-Gillam, Andrea / Li, Chung-Pin / Bodoky, György / Dean, Andrew P / Shan, Yan-Shen / Jameson, Gayle S / Macarulla, Teresa / Lee, Kyung-Hun / Cunningham, David / Blanc, Jean-Frédéric / Chiu, Chang-Fang / Schwartsmann, Gilberto / Braiteh, Fadi S / Mamlouk, Khalid / Belanger, Bruce / de Jong, Floris A / Hubner, Richard A. ·National Institute of Cancer Research, National Health Research Institutes (NHRI), 367 Sheng-Li Road, Tainan 704, Taiwan; Department of Internal Medicine, National Cheng Kung University Hospital, National Cheng Kung University, No. 138, Sheng-Li Road, Tainan 704, Taiwan. Electronic address: leochen@nhri.org.tw. · Division of Solid Tumor Translational Oncology, West German Cancer Center, University Hospital Essen, Hufelandstrasse 55, 45147 Essen, Germany; German Cancer Consortium (DKTK, Partner Site Essen) and German Cancer Research Center, DKFZ, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany. · Division of Oncology, Washington University in St. Louis, 660 South Euclid Ave, St. Louis, MO 63110, USA. · Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, No. 201, Section 2, Shipai Rd, Beitou District, Taipei 112, Taiwan; National Yang-Ming University School of Medicine, No. 155, Section 2, Linong St, Beitou District, Taipei 112, Taiwan. · Department of Oncology, Szent László Hospital, Albert Flórián út 5, 1097 Budapest, Hungary. · St. John of God Hospital, 12 Salvado Rd, Subiaco, WA 6008, Australia. · Department of Surgery, National Cheng Kung University Hospital, No. 138, Shengli Rd, North District, Tainan 704, Taiwan. · Virginia G. Piper Cancer Center at HonorHealth/TGen, 10460N 92(nd) St #206, Scottsdale, AZ 85258, USA. · Vall d'Hebron University Hospital (HUVH), Passeig de la Vall d'Hebron, 119-129, 08035 Barcelona, Spain; Vall d'Hebron Institute of Oncology (VHIO), Centro Cellex, Calle Natzaret, 115-117, 08035 Barcelona, Spain. · Department of Internal Medicine and Cancer Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, 1 Gwanak-ro, Daehak-dong, Gwanak-gu, Seoul 03080, South Korea. · The Royal Marsden Hospital NHS Foundation Trust, 203 Fulham Rd, Chelsea, SW3 6JJ London, UK; The Royal Marsden Hospital NHS Foundation Trust (Surrey), Downs Rd, Sutton, SM2 5PT Surrey, UK. · Pôle ADEN, Hôpital Haut-Lévêque, CHU Bordeaux, 33075 Bordeaux, France. · China Medical University Hospital, No. 2, Yuh-Der Rd, Taichung 404, Taiwan. · Federal University of Rio Grande do Sul, Av. Paulo Gama, 110 - Farroupilha, Porto Alegre, RS 90040-060, Brazil. · Comprehensive Cancer Centers of Nevada, University of Nevada School of Medicine, 3730 S Eastern Ave, Las Vegas, NV 89169, USA. · Ipsen Bioscience, Inc., 650 East Kendall St, Cambridge, MA 02142, USA. · Shire, Zählerweg 10, 6300 Zug, Switzerland. · Department of Medical Oncology, The Christie Hospital NHS Foundation Trust, 550 Wilmslow Rd, M20 4BX Manchester, UK. ·Eur J Cancer · Pubmed #30414528.

ABSTRACT: BACKGROUND: In the phase 3 randomised NAPOLI-1 clinical study, a 45% increase in median overall survival (OS) was shown with liposomal irinotecan, 5-fluorouracil and leucovorin (nal-IRI+5-FU/LV) versus 5-FU/LV in patients with metastatic pancreatic cancer progressing after gemcitabine-based therapy. Here, we report data from a pre-specified, expanded analysis of outcomes in the per-protocol (PP) population. MATERIALS AND METHODS: The PP population comprised patients receiving ≥80% of planned treatment during the first 6 weeks, with no major protocol violations. A post-hoc analysis of the non-PP population was also performed. RESULTS: For PP patients, median OS was 8.9 (95% confidence interval: 6.4-10.5) months with nal-IRI+5-FU/LV (n = 66) vs 5.1 (4.0-7.2) months with 5-FU/LV (n = 71; unstratified hazard ratio [HR] 0.57, p = 0.011). For non-PP patients, it was 4.4 (3.3-5.3) months with nal-IRI+5-FU/LV (n = 51) vs 2.8 (1.7-3.2) months with 5-FU/LV (n = 48; unstratified HR 0.64, p = 0.0648). CONCLUSION: A statistically significant survival advantage was observed with nal-IRI+5-FU/LV vs 5-FU/LV in the PP patient population.

14 Clinical Trial Efficacy of gemcitabine plus erlotinib in rash-positive patients with metastatic pancreatic cancer selected according to eligibility for FOLFIRINOX: A prospective phase II study of the 'Arbeitsgemeinschaft Internistische Onkologie'. 2018

Haas, M / Siveke, J T / Schenk, M / Lerch, M M / Caca, K / Freiberg-Richter, J / Fischer von Weikersthal, L / Kullmann, F / Reinacher-Schick, A / Fuchs, M / Kanzler, S / Kunzmann, V / Ettrich, T J / Kruger, S / Westphalen, C B / Held, S / Heinemann, V / Boeck, S. ·Department of Medicine III, University Hospital, LMU Munich, Munich, Germany. Electronic address: michael.haas@med.lmu.de. · 2nd Medical Department, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany; German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany; Division of Solid Tumor Translational Oncology (DKTK, Partner Site Essen), West German Cancer Center, University Hospital Essen, Essen, Germany. · Department of Haematology and Oncology, Hospital Barmherzige Brüder, Regensburg, Germany. · Department of Medicine A, Universitätsmedizin Greifswald, Ernst-Moritz-Arndt University, Greifswald, Germany. · Department of Internal Medicine I, Klinikum Ludwigsburg, Ludwigsburg, Germany. · Practice for Haematology and Oncology, Dresden, Germany. · Department of Oncology, Gesundheitszentrum St. Marien, Amberg, Germany. · Department of Medicine I, Klinikum Weiden, Weiden, Germany. · Department of Haematology and Oncology, St. Josef-Hospital, Ruhr University, Bochum, Germany. · Department of Gastroenterology, Hepatology and Gastrointestinal Oncology, Klinikum Bogenhausen, Munich, Germany. · Department of Internal Medicine II, Leopoldina Krankenhaus Schweinfurt, Schweinfurt, Germany. · Department of Medical Oncology, University Hospital of Wuerzburg, Wuerzburg, Germany. · Department of Internal Medicine I, University of Ulm, Ulm, Germany. · Department of Medicine III, University Hospital, LMU Munich, Munich, Germany. · ClinAssess GmbH, Leverkusen, Germany. ·Eur J Cancer · Pubmed #29549862.

ABSTRACT: INTRODUCTION: In metastatic pancreatic ductal adenocarcinoma (mPDAC) treatment, erlotinib is known to be more effective in patients developing skin rash. Treatment with the FOLFIRINOX regimen is only performed in fit patients following defined inclusion criteria. The present study investigates the efficacy of gemcitabine plus erlotinib (gem/erlotinib) in rash-positive patients fit for FOLFIRINOX. PATIENTS AND METHODS: For this prospective phase II study, 150 patients were recruited in 20 centres. All patients received gem/erlotinib for 4 weeks (run-in phase); the subsequent treatment was determined by the development of skin rash: patients with rash grades 1-4 continued with gem/erlotinib, rash-negative patients were switched to FOLFIRINOX. Primary study end-point was to achieve a 1-year survival rate in rash-positive patients ≥40%. RESULTS: Ninety patients were deemed positive for skin rash by the end of the run-in phase, showing a 1-year survival rate of 40.0% (95% confidence interval [CI] 29.8-50.9). Median overall survival (OS) was 10.1 months, progression-free survival (PFS) was 3.8 months and overall response rate (ORR) was 23.3%. Patients switched to FOLFIRINOX (n = 27) had a 1-year survival rate of 48.1% (95% CI 28.7-68.1), a median OS of 10.9 months, a median PFS of 6.6 months and an ORR of 33.3%. Rash-negative patients had a lower quality of life at baseline but seemed to experience an improved control of pain during FOLFIRINOX. CONCLUSIONS: First-line treatment with gem/erlotinib was effective in fit, rash-positive mPDAC patients achieving a 1-year survival rate comparable to previous reports for FOLFIRINOX. The study was registered at clinicaltrials.gov (NCT0172948) and Eudra-CT (2011-005471-17).

15 Clinical Trial Gemcitabine combined with the monoclonal antibody nimotuzumab is an active first-line regimen in KRAS wildtype patients with locally advanced or metastatic pancreatic cancer: a multicenter, randomized phase IIb study. 2017

Schultheis, B / Reuter, D / Ebert, M P / Siveke, J / Kerkhoff, A / Berdel, W E / Hofheinz, R / Behringer, D M / Schmidt, W E / Goker, E / De Dosso, S / Kneba, M / Yalcin, S / Overkamp, F / Schlegel, F / Dommach, M / Rohrberg, R / Steinmetz, T / Bulitta, M / Strumberg, D. ·Department of Hematology/Oncology, University Bochum, Marien Hospital Herne, Herne. · Oncoscience AG, Wedel. · Klinikum Rechts der Isar TU München, München. · University Hospital Münster, Münster. · Department of Hematology and Medical Oncology, University Medical Center Mannheim, Mannheim. · Augusta-Kranken-Anstalt, Bochum. · St. Josef Hospital, Med. Klinik I, Bochum, Germany. · Ege University Medical School, Izmir, Turkey. · Oncology Institute of Southern Switzerland, Bellinzona, Switzerland. · Department of Medicine, University Medical Center Schleswig-Holstein, Kiel, Germany. · Hacettepe University Hospital, Ankara, Turkey. · Medical Practice for Oncology and Hematology, Recklinghausen. · St. Antonius Hospital, Eschweiler. · Sana-Kliniken, Medizinisches Versorgungszentrum Onkologie, Düsseldorf. · Gemeinschaftspraxis und Tagesklinik fuer Haematologie, Onkologie und Gastroenterologie, Halle. · Group Practice Hematology/Oncology Cologne, Cologne. · CRM Biometrics GmbH, Rheinbach, Germany. ·Ann Oncol · Pubmed #28961832.

ABSTRACT: Background: This randomized study was designed to investigate the superiority of gemcitabine (gem) plus nimotuzumab (nimo), an anti-epidermal growth factor receptor monoclonal antibody, compared with gem plus placebo as first-line therapy in patients with advanced pancreatic cancer. Patients and methods: Patients with previously untreated, unresectable, locally advanced or metastatic pancreatic cancer were randomly assigned to receive gem: 1000 mg/m2, 30-min i.v. once weekly (d1, 8, 15; q29) and nimo: fixed dose of 400 mg once weekly as a 30-min infusion, or gem plus placebo, until progression or unacceptable toxicity. The primary end point was overall survival (OS), secondary end points included time to progression, overall response rate, safety and quality of life. Results: A total of 192 patients were randomized, with 186 of them being assessable for efficacy and safety (average age 63.6 years). One-year OS/progression-free survival (PFS) was 34%/22% for gem plus nimo compared with 19%/10% for gem plus placebo (HR = 0.69; P = 0.03/HR = 0.68; P = 0.02). Median OS/PFS was 8.6/5.1 months for gem plus nimo versus 6.0/3.4 mo in the gem plus placebo group (HR = 0.69; P = 0.0341/HR = 0.68; P = 0.0163), with very few grade 3/4 toxicities. KRAS wildtype patients experienced a significantly better OS than those with KRAS mutations (11.6 versus 5.6 months, P = 0.03). Conclusion: This randomized study showed that nimo in combination with gem is safe and well tolerated. The 1-year OS and PFS rates for the entire population were significantly improved. Especially, those patients with KRAS wildtype seem to benefit. The study was registered as protocol ID OSAG101-PCS07, NCT00561990 and EudraCT 2007-000338-38.

16 Clinical Trial Quality-adjusted survival with combination nal-IRI+5-FU/LV vs 5-FU/LV alone in metastatic pancreatic cancer patients previously treated with gemcitabine-based therapy: a Q-TWiST analysis. 2017

Pelzer, Uwe / Blanc, Jean-Frédéric / Melisi, Davide / Cubillo, Antonio / Von Hoff, Daniel D / Wang-Gillam, Andrea / Chen, Li-Tzong / Siveke, Jens T / Wan, Yin / Solem, Caitlyn T / Botteman, Marc F / Yang, Yoojung / de Jong, Floris A / Hubner, Richard A. ·Department of Hematology/Oncology/Tumorimmunology, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany. · Service d'Hépato-Gastroentérologie et Oncologie Digestive, Hôpital Haut-Lévêque, CHU de Bordeaux, Inserm UMR 1053, Université de Bordeaux, Bordeaux, France. · Digestive Molecular Clinical Oncology Unit, University of Verona, Piazzale L.A. Scuro, 10, 37134 Verona, Italy. · Servicio de Oncologia Médica, Centro Integral Oncológico Clara Campal (CIOCC), Hospital Universitario Madrid Sanchinarro, Calle Oña, 10, 28050 Madrid, Spain. · Virginia G. Piper Cancer Center at HonorHealth/TGen, 10460N 92nd St #206, Scottsdale, AZ 85258, USA. · Division of Oncology, Washington University in St Louis, 660 South Euclid Avenue, St Louis, MO 63110, USA. · National Institute of Cancer Research, National Health Research Institutes, 2F, No. 367, Sheng-Li Road, Tainan 70456, Taiwan. · Division of Solid Tumor Translational Oncology, DKTK Partner Site Essen, West German Cancer Center, University Hospital Essen, Hufelandstrasse 55, 45147 Essen, Germany. · German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany. · Pharmerit International, 4350 East-West Hwy #430, Bethesda, MD 20814, USA. · Shire, Plc, 650 East Kendal St, Cambridge, MA 02142, USA. · Department of Global Medical Affairs Oncology, Shire GmbH, Zählerweg 10, 6300 Zug, Switzerland. · Department of Medical Oncology, Christie Hospital NHS Foundation Trust, 550 Wilmslow Rd, Manchester M20 4BX, UK. ·Br J Cancer · Pubmed #28350787.

ABSTRACT: BACKGROUND: In the NAPOLI-1 Phase 3 trial, nal-IRI+5-fluorouracil and leucovorin (5-FU/LV) significantly improved median overall survival (6.1 vs 4.2 months, P=0.012) and progression-free survival (3.1 vs 1.5 months, P=0.0001) vs 5-FU/LV alone in metastatic pancreatic adenocarcinoma patients previously treated with gemcitabine-based therapy. This analysis evaluated between treatment differences in quality-adjusted time without symptoms of disease progression or toxicity (Q-TWiST). METHODS: Overall survival was partitioned into time with grade ⩾3 toxicity (TOX), disease progression (REL), and time without disease progression symptoms or grade ⩾3 toxicity (TWiST). Mean Q-TWiST was calculated by weighting time spent by a utility of 1.0 for TWiST and 0.5 for TOX and REL. In threshold analyses, utility for TOX and REL were varied from 0.0 to 1.0. RESULTS: Patients in nal-IRI+5-FU/LV (n=117) vs 5-FU/LV (n=119) had significantly more mean time in TWiST (3.4 vs 2.4 months) and TOX (1.0 vs 0.3 months) but similar REL (2.5 vs 2.7 months). In the base case, nal-IRI+5-FU/LV patients had 1.3 months (95% CI, 0.4-2.1; 5.1 vs 3.9) greater Q-TWiST (threshold analyses range: 0.9-1.6 months). CONCLUSIONS: Within NAPOLI-1, nal-IRI+5-FU/LV resulted in statistically significant and clinically meaningful gains in quality-adjusted survival vs 5-FU/LV alone.

17 Clinical Trial Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1): a global, randomised, open-label, phase 3 trial. 2016

Wang-Gillam, Andrea / Li, Chung-Pin / Bodoky, György / Dean, Andrew / Shan, Yan-Shen / Jameson, Gayle / Macarulla, Teresa / Lee, Kyung-Hun / Cunningham, David / Blanc, Jean F / Hubner, Richard A / Chiu, Chang-Fang / Schwartsmann, Gilberto / Siveke, Jens T / Braiteh, Fadi / Moyo, Victor / Belanger, Bruce / Dhindsa, Navreet / Bayever, Eliel / Von Hoff, Daniel D / Chen, Li-Tzong / Anonymous2510850. ·Washington University School of Medicine, St Louis, MO, USA. · Division of Gastroenterology and Hepatology, Taipei Veterans General Hospital and National Yang-Ming University School of Medicine, Taipei, Taiwan. · St László Teaching Hospital, Budapest, Hungary. · St John of God Hospital, Subiaco, WA, Australia. · National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan. · TGen, Phoenix, and HonorHealth, Scottsdale, AZ, USA. · Vall d'Hebron University Hospital (HUVH) and Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. · Seoul National University Hospital, Seoul, South Korea. · The Royal Marsden Hospital, London, UK. · Hôpital Saint-André, Bordeaux, France. · The Christie NHS Foundation Trust, Manchester, UK. · China Medical University Hospital, Taichung, Taiwan. · Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil. · Klinikum rechts der Isar der T U München, Munich, Germany. · Comprehensive Cancer Centers of Nevada, Las Vegas, NV, USA. · Merrimack Pharmaceuticals, Cambridge, MA, USA. · National Institute of Cancer Research, National Health Research Institutes, Tainan, and Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan. Electronic address: leochen@nhri.org.tw. ·Lancet · Pubmed #26615328.

ABSTRACT: BACKGROUND: Nanoliposomal irinotecan showed activity in a phase 2 study in patients with metastatic pancreatic ductal adenocarcinoma previously treated with gemcitabine-based therapies. We assessed the effect of nanoliposomal irinotecan alone or combined with fluorouracil and folinic acid in a phase 3 trial in this population. METHODS: We did a global, phase 3, randomised, open-label trial at 76 sites in 14 countries. Eligible patients with metastatic pancreatic ductal adenocarcinoma previously treated with gemcitabine-based therapy were randomly assigned (1:1) using an interactive web response system at a central location to receive either nanoliposomal irinotecan monotherapy (120 mg/m(2) every 3 weeks, equivalent to 100 mg/m(2) of irinotecan base) or fluorouracil and folinic acid. A third arm consisting of nanoliposomal irinotecan (80 mg/m(2), equivalent to 70 mg/m(2) of irinotecan base) with fluorouracil and folinic acid every 2 weeks was added later (1:1:1), in a protocol amendment. Randomisation was stratified by baseline albumin, Karnofsky performance status, and ethnic origin. Treatment was continued until disease progression or intolerable toxic effects. The primary endpoint was overall survival, assessed in the intention-to-treat population. The primary analysis was planned after 305 events. Safety was assessed in all patients who had received study drug. This trial is registered at ClinicalTrials.gov, number NCT01494506. FINDINGS: Between Jan 11, 2012, and Sept 11, 2013, 417 patients were randomly assigned either nanoliposomal irinotecan plus fluorouracil and folinic acid (n=117), nanoliposomal irinotecan monotherapy (n=151), or fluorouracil and folinic acid (n=149). After 313 events, median overall survival in patients assigned nanoliposomal irinotecan plus fluorouracil and folinic acid was 6.1 months (95% CI 4.8-8.9) vs 4.2 months (3.3-5.3) with fluorouracil and folinic acid (hazard ratio 0.67, 95% CI 0.49-0.92; p=0.012). Median overall survival did not differ between patients assigned nanoliposomal irinotecan monotherapy and those allocated fluorouracil and folinic acid (4.9 months [4.2-5.6] vs 4.2 months [3.6-4.9]; 0.99, 0.77-1.28; p=0.94). The grade 3 or 4 adverse events that occurred most frequently in the 117 patients assigned nanoliposomal irinotecan plus fluorouracil and folinic acid were neutropenia (32 [27%]), diarrhoea (15 [13%]), vomiting (13 [11%]), and fatigue (16 [14%]). INTERPRETATION: Nanoliposomal irinotecan in combination with fluorouracil and folinic acid extends survival with a manageable safety profile in patients with metastatic pancreatic ductal adenocarcinoma who previously received gemcitabine-based therapy. This agent represents a new treatment option for this population. FUNDING: Merrimack Pharmaceuticals.

18 Clinical Trial pERK, pAKT and p53 as tissue biomarkers in erlotinib-treated patients with advanced pancreatic cancer: a translational subgroup analysis from AIO-PK0104. 2014

Ormanns, Steffen / Siveke, Jens T / Heinemann, Volker / Haas, Michael / Sipos, Bence / Schlitter, Anna Melissa / Esposito, Irene / Jung, Andreas / Laubender, Rüdiger P / Kruger, Stephan / Vehling-Kaiser, Ursula / Winkelmann, Cornelia / Fischer von Weikersthal, Ludwig / Clemens, Michael R / Gauler, Thomas C / Märten, Angela / Geissler, Michael / Greten, Tim F / Kirchner, Thomas / Boeck, Stefan. ·Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, München, Germany. stefan.boeck@med.uni-muenchen.de. ·BMC Cancer · Pubmed #25164437.

ABSTRACT: BACKGROUND: The role of pERK, pAKT and p53 as biomarkers in patients with advanced pancreatic cancer has not yet been defined. METHODS: Within the phase III study AIO-PK0104 281 patients with advanced pancreatic cancer received an erlotinib-based 1st-line regimen. Archival tissue from 153 patients was available for central immunohistochemistry staining for pERK, pAKT and p53. Within a subgroup analysis, biomarker data were correlated with efficacy endpoints and skin rash using a Cox regression model. RESULTS: Fifty-five out of 153 patients were classified as pERKlow and 98 patients as pERKhigh; median overall survival (OS) was 6.2 months and 5.7 months, respectively (HR 1.29, p = 0.16). When analysing pERK as continuous variable, the pERK score was significantly associated with OS (HR 1.06, 95% CI 1.0-1.12, p = 0.05). Twenty-one of 35 patients were pAKTlow and 14/35 pAKThigh with a corresponding median OS of 6.4 months and 6.8 months, respectively (HR 1.03, p = 0.93). Four out of 50 patients had a complete loss of p53 expression, 20 patients a regular expression and 26 patients had tumors with p53 overexpression. The p53 status had no impact on OS (p = 0.91); however, a significant improvement in progression-free survival (PFS) (6.0 vs 1.8 months, HR 0.24, p = 0.02) and a higher rate of skin rash (84% vs 25%, p = 0.02) was observed for patients with a regular p53 expression compared to patients with a complete loss of p53. CONCLUSION: pERK expression may have an impact on OS in erlotinib-treated patients with advanced pancreatic cancer; p53 should be further investigated for its potential role as a predictive marker for PFS and skin rash. TRIAL REGISTRATION: NCT00440167 (registration date: February 22, 2007).

19 Article Nomogram for Predicting Survival in Patients Treated with Liposomal Irinotecan Plus Fluorouracil and Leucovorin in Metastatic Pancreatic Cancer. 2019

Chen, Li-Tzong / Macarulla, Teresa / Blanc, Jean-Frédéric / Mirakhur, Beloo / Jong, Floris A de / Belanger, Bruce / Bekaii-Saab, Tanios / Siveke, Jens T. ·National Institute of Cancer Research, National Health Research Institutes, 704 Tainan, Taiwan. leochen@nhri.org.tw. · Division of Hematology/Oncology, Department of Internal Medicine, National Cheng Kung University Hospital, 704 Tainan, Taiwan. leochen@nhri.org.tw. · Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology, 08035 Barcelona, Spain. · Groupe Hospitalier Haut-Lévêque, CHU Bordeaux, 33600 Pessac, France. · Ipsen Biopharmaceuticals, Inc., Basking Ridge, NJ 07920, USA. · Global Medical Affiars, Servier, 8002 Zürich, Switzerland. · Ipsen Biopharmaceuticals, Inc., Cambridge, MA 02142, USA. · Mayo Clinic Cancer Center, Phoenix, AZ 85054, USA. · German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany. · West German Cancer Center, University Hospital Essen, 45147 Essen, Germany. ·Cancers (Basel) · Pubmed #31357748.

ABSTRACT: NAPOLI-1 (NCT01494506) was a phase III study of liposomal irinotecan (nal-IRI) plus 5-fluorouracil/leucovorin (5-FU/LV) in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) previously treated with gemcitabine-based therapy. This post hoc analysis of NAPOLI-1 aimed to develop a predictive nomogram for overall survival (OS) at 6 and 12 months. Analyses were derived from all patients in NAPOLI-1 randomized to receive nal-IRI+5-FU/LV, nal-IRI monotherapy, or 5-FU/LV combination therapy. OS was associated with baseline factors using univariate and multivariable Cox analyses. A predictive nomogram was derived and validated using a concordance index and calibration plots. The univariate analyses identified 21 independent factors that contributed to OS, with eight factors significantly associated with OS. The Karnofsky Performance Score contributed the largest number of points (100), followed by presence of liver metastasis (98) and randomization to nal-IRI+5-FU/LV (96). The other baseline factors showing effects were albumin (g/dL), neutrophil/lymphocyte ratio, carbohydrate antigen 19-9 (U/mL), disease stage at diagnosis, and body mass index (kg/m

20 Article Liposomal irinotecan and 5-fluorouracil/leucovorin in older patients with metastatic pancreatic cancer - A subgroup analysis of the pivotal NAPOLI-1 trial. 2019

Macarulla, Teresa / Blanc, Jean-Frédéric / Wang-Gillam, Andrea / Chen, Li-Tzong / Siveke, Jens T / Mirakhur, Beloo / Chen, Jie / de Jong, Floris A. ·Vall d'Hebron University Hospital (HUVH), Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. Electronic address: tmacarulla@vhebron.net. · Pôle ADEN, Hôpital Haut-Lévêque, CHU Bordeaux, Bordeaux, France. · Division of Oncology, Washington University in St. Louis, MO, USA. · National Institute of Cancer Research, National Health Research Institutes, National Cheng Kung University, Tainan, Taiwan; Department of Internal Medicine, National Cheng Kung University, Tainan, Taiwan. · Division of Solid Tumor Translational Oncology, West German Cancer Center, University Hospital Essen, Essen, Germany; Cancer Consortium (DKTK, partner site Essen), German Cancer Research Center, DKFZ, Heidelberg, Germany. · Ipsen Biopharmaceuticals, Inc., Cambridge, MA, United States. · Shire plc, Cambridge, MA, United States. · Global Medical Affairs, Servier, Zurich, Switzerland. ·J Geriatr Oncol · Pubmed #30842038.

ABSTRACT: OBJECTIVES: Pancreatic cancer is a highly lethal disease predominantly affecting older patients. Characterization of outcomes in these patients may help optimise treatment decisions. The global, phase 3 NAPOLI-1 trial (NCT01494506) demonstrated an overall survival (OS) benefit with liposomal irinotecan and 5-flurouracil/leucovorin (nal-IRI + 5-FU/LV) versus 5-FU/LV. This subgroup analysis explored impact of age on outcomes in NAPOLI-1 patients, and nal-IRI + 5-FU/LV efficacy and safety in older patients. MATERIALS AND METHODS: This exploratory, post-hoc analysis of the NAPOLI-1 trial included patients aged ≥eighteen years (no upper limit) with metastatic pancreatic adenocarcinoma that had progressed on gemcitabine-based therapy. Patients were stratified by age (cut-offs at 65, 70, and 75 years); OS and progression-free survival (PFS) were estimated by Kaplan-Meier analysis. RESULTS: Of 417 randomized patients, 192 (46%), 110 (26%) and 43 (10%) were aged ≥65, ≥70 and ≥ 75 years, respectively. Mortality risk and risk of disease progression were similar in older and younger patients independent of treatment (HRs for median [m]OS/mPFS comparisons were 0.88/0.95 [<65 versus ≥65 years], 0.89/0.88 [<70 versus ≥70 years] and 1.04/0.98 [<75 versus ≥75 years]; P > .25). Reduced mortality/morbidity risk with nal-IRI + 5-FU/LV in older subgroups was in line with the wider population. No additional toxicities with nal-IRI + 5-FU/LV were observed in older patients: 86% of patients ≥75 years versus 69% <75 years required a dose delay or reduction due to toxicities (43% versus 32% dose reductions). DISCUSSION: Results suggest that older patients with metastatic pancreatic adenocarcinoma that progressed on prior gemcitabine-based treatment can benefit from second-line therapy, supporting nal-IRI + 5-FU/LV treatment in older patients.

21 Article Still a hopeless case for personalized oncology? Pancreatic cancer revisited. 2019

Weichert, Wilko / Sprick, Martin R / Siveke, Jens T. ·Member of the German Cancer Consortium (DKTK), Institute of Pathology, Technical University Munich, 81675 Munich, Germany. ·Oncoscience · Pubmed #30800713.

ABSTRACT: -- No abstract --

22 Article Quality of life in metastatic pancreatic cancer patients receiving liposomal irinotecan plus 5-fluorouracil and leucovorin. 2019

Hubner, Richard A / Cubillo, Antonio / Blanc, Jean-Frédéric / Melisi, Davide / Von Hoff, Daniel D / Wang-Gillam, Andrea / Chen, Li-Tzong / Becker, Claus / Mamlouk, Khalid / Belanger, Bruce / Yang, Yoojung / de Jong, Floris A / Siveke, Jens T. ·Department of Medical Oncology, The Christie NHS Foundation Trust, 550 Wilmslow Rd, Manchester, M20 4BX, UK. Electronic address: Richard.Hubner@christie.nhs.uk. · Centro Integral Oncológico Clara Campal (CIOCC), HM Universitario Madrid Sanchinarro, C/ Oña, 10, 28050, Madrid, Spain; Departamento de Ciencias Médicas Clínicas, Universidad CEU San Pablo, C/ Oña, 10, 28050, Madrid, Spain. · Hepato-Gastroentertology and Digestive Oncology Unit, Hôpital Haut-Lévêque, CHU Bordeaux, Av. Magellan, 33600, Pessac, France. · Digestive Molecular Clinical Oncology Unit, University of Verona, Piazzale L.A. Scuro, 10, 37134, Verona, Italy. · Translational Genomics Research Institute and Honor Health, 10510 N 92nd St, #200, Scottsdale, AZ, 85258, USA. · Washington University in St. Louis, 1 Brookings Dr, St. Louis, MO, 63130, USA. · National Institute of Cancer Research, National Health Research Institutes (NHRI), 367 Sheng-Li Road, Tainan, 704, Taiwan. · Merrimack Pharmaceuticals, Inc., 1 Kendall Square, B7201, Cambridge, MA, 02139, USA. · Ipsen Biopharmaceuticals, Inc., 650 E. Kendall Street, Cambridge, MA, 02142, USA. · Shire, Zählerweg 10, 6300, Zug, Switzerland. · Division of Solid Tumor Translational Oncology, West German Cancer Center, University Hospital Essen, Hufelandstrasse 55, 45147, Essen, Germany; German Cancer Consortium (DKTK, Partner Site Essen) and German Cancer Research Center, DKFZ, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany. ·Eur J Cancer · Pubmed #30458340.

ABSTRACT: BACKGROUND: The NAPOLI-1 study (NCT01494506) reported that liposomal irinotecan plus 5-fluorouracil and leucovorin (nal-IRI+5-FU/LV) improved overall survival vs 5-FU/LV with manageable toxicity in patients with metastatic pancreatic adenocarcinoma previously treated with gemcitabine-based therapy. Yet, clinicians need treatment strategies that also maintain the patient's health-related quality of life (HRQOL). Here, we report the HRQOL data. METHODS: Patients completed the European Organisation for Research and Treatment of Cancer QOL core questionnaire C30 (EORTC QLQ-C30) at baseline, every 6 weeks, and at 30 days after discontinuation of study treatment. Patient-reported outcomes (PROs) were scored according to EORTC guidelines. nal-IRI+5-FU/LV HRQOL was compared with 5-FU/LV. The PRO population comprised intent-to-treat patients who completed baseline and at least one subsequent assessment on the EORTC QLQ-C30. Data were also analysed for missingness. RESULTS: Of 236 patients in the intent-to-treat population, 128 (54.2%) comprised the PRO population (71 in the nal-IRI+5-FU/LV arm; 57 the in 5-FU/LV arm). Of the remaining 108 patients (45.8%) not included in the PRO population, most progressed rapidly, making participation difficult. Median change from baseline was ≤10 points at weeks 6 and 12 in global health status or functional and symptom scale scores, except for fatigue, which deteriorated by 11.1 points with nal-IRI+5-FU/LV but did not change vs 5-FU/LV. The proportion of patients whose HRQOL improved or deteriorated was not significantly different between the arms. CONCLUSION: In the NAPOLI-1 study, HRQOL was maintained with nal-IRI+5-FU/LV in patients with metastatic pancreatic adenocarcinoma previously treated with a gemcitabine-based regimen, while survival was significantly extended.

23 Article A Novel Approach for Image-Guided 2019

Schug, Christina / Gupta, Aayush / Urnauer, Sarah / Steiger, Katja / Cheung, Phyllis Fung-Yi / Neander, Christian / Savvatakis, Konstantinos / Schmohl, Kathrin A / Trajkovic-Arsic, Marija / Schwenk, Nathalie / Schwaiger, Markus / Nelson, Peter J / Siveke, Jens T / Spitzweg, Christine. ·Department of Internal Medicine IV, University Hospital of Munich, Ludwig-Maximilians-University Munich, Munich, Germany. · Department of Internal Medicine II, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany. · Institute of Pathology, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany. · Division of Solid Tumor Translational Oncology, West German Cancer Center, University Hospital Essen, Essen, Germany. · German Cancer Consortium (DKTK), partner site Essen and German Cancer Research Center (DKFZ), Heidelberg, Germany. · Department of Nuclear Medicine, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany. · Clinical Biochemistry Group, Department of Internal Medicine IV, University Hospital of Munich, Ludwig-Maximilians-University Munich, Munich, Germany. · Department of Internal Medicine IV, University Hospital of Munich, Ludwig-Maximilians-University Munich, Munich, Germany. Christine.Spitzweg@med.uni-muenchen.de. ·Mol Cancer Res · Pubmed #30224540.

ABSTRACT: The sodium iodide symporter (

24 Article Notch-Induced Myeloid Reprogramming in Spontaneous Pancreatic Ductal Adenocarcinoma by Dual Genetic Targeting. 2018

Cheung, Phyllis F / Neff, Florian / Neander, Christian / Bazarna, Anna / Savvatakis, Konstantinos / Liffers, Sven-Thorsten / Althoff, Kristina / Lee, Chang-Lung / Moding, Everett J / Kirsch, David G / Saur, Dieter / Bazhin, Alexandr V / Trajkovic-Arsic, Marija / Heikenwalder, Mathias F / Siveke, Jens T. ·Division of Solid Tumor Translational Oncology, West German Cancer Center, University Hospital Essen, Essen, Germany. · German Cancer Consortium (DKTK, partner site Essen) and German Cancer Research Center, DKFZ, Heidelberg, Germany. · Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina. · Medical Department, Klinikum rechts der Isar, Technische Universität München, Munich, Germany. · Department of General, Visceral and Transplant Surgery, Ludwig-Maximilians University, Munich, Germany. · German Caner Consortium (DKTK), Partner Site Munich, Germany. · Division of Chronic Inflammation and Cancer, DKFZ, Heidelberg, Germany. · Division of Solid Tumor Translational Oncology, West German Cancer Center, University Hospital Essen, Essen, Germany. j.siveke@dkfz.de. ·Cancer Res · Pubmed #29844119.

ABSTRACT: Despite advances in our understanding of the genetics of pancreatic ductal adenocarcinoma (PDAC), the efficacy of therapeutic regimens targeting aberrant signaling pathways remains highly limited. Therapeutic strategies are greatly hampered by the extensive desmoplasia that comprises heterogeneous cell populations. Notch signaling is a contentious pathway exerting opposite roles in tumorigenesis depending on cellular context. Advanced model systems are needed to gain more insights into complex signaling in the multilayered tumor microenvironment. In this study, we employed a dual recombinase-based

25 Article Apparent Diffusion Coefficient (ADC) predicts therapy response in pancreatic ductal adenocarcinoma. 2017

Trajkovic-Arsic, M / Heid, I / Steiger, K / Gupta, A / Fingerle, A / Wörner, C / Teichmann, N / Sengkwawoh-Lueong, S / Wenzel, P / Beer, A J / Esposito, I / Braren, R / Siveke, J T. ·Division of Solid Tumor Translational Oncology, West German Cancer Center, University Hospital Essen, Essen, Germany. · German Cancer Consortium (DKTK, partner site Essen) and German Cancer Research Center (DKFZ), Heidelberg, Germany. · Institute of Radiology, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany. · Institute of Pathology, TUM School of Medicine, Technical University of Munich, Munich, Germany. · 2. Medizinische Klinik, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany. · Department of Nuclear Medicine, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany. · Department of Nuclear Medicine, University Hospital of Ulm, Ulm, Germany. · Institute of Pathology, University Clinic Duesseldorf, Heinrich-Heine University, Duesseldorf, Germany. · Institute of Radiology, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany. rbraren@tum.de. · Division of Solid Tumor Translational Oncology, West German Cancer Center, University Hospital Essen, Essen, Germany. j.siveke@dkfz.de. · German Cancer Consortium (DKTK, partner site Essen) and German Cancer Research Center (DKFZ), Heidelberg, Germany. j.siveke@dkfz.de. · 2. Medizinische Klinik, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany. j.siveke@dkfz.de. ·Sci Rep · Pubmed #29213099.

ABSTRACT: Recent advances in molecular subtyping of Pancreatic Ductal Adenocarcinoma (PDAC) support individualization of therapeutic strategies in this most aggressive disease. With the emergence of various novel therapeutic strategies and neoadjuvant approaches in this quickly deteriorating disease, robust approaches for fast evaluation of therapy response are urgently needed. To this aim, we designed a preclinical imaging-guided therapy trial where genetically engineered mice harboring endogenous aggressive PDAC were treated with the MEK targeting drug refametinib, which induces rapid and profound tumor regression in this model system. Multi-parametric non-invasive imaging was used for therapy response monitoring. A significant increase in the Diffusion-Weighted Magnetic Resonance Imaging derived Apparent Diffusion Coefficient (ADC) was noted already 24 hours after treatment onset. Histopathological analyses showed increased apoptosis and matrix remodeling at this time point. Our findings suggest the ADC parameter as an early predictor of therapy response in PDAC.

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