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Pancreatic Neoplasms: HELP
Articles by David Goldstein
Based on 39 articles published since 2008
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Between 2008 and 2019, David Goldstein wrote the following 39 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2
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 Review Current challenges in optimizing systemic therapy for patients with pancreatic cancer: expert perspectives from the Australasian Gastrointestinal Trials Group (AGITG) with invited international faculty. 2017

Segelov, Eva / Lordick, Florian / Goldstein, David / Chantrill, Lorraine A / Croagh, Daniel / Lawrence, Ben / Arnold, Dirk / Chau, Ian / Obermannova, Radka / Price, Timothy Jay. ·a Department of Oncology , Monash Medical Centre and Monash University , Melbourne , Australia. · b Department of Oncology, University Cancer Center Leipzig , University Medicine Leipzig , Leipzig , Germany. · c Department of Oncology, Nelune Cancer Centre , Prince of Wales Hospital and University of New South Wales , Sydney , Australia. · d Department of Oncology , The Kinghorn Cancer Centre and University of Western Sydney , Sydney , Australia. · e Department of Oncology , University of Auckland , Auckland , New Zealand. · f Department of Oncology , Instituto CUF de Oncologia , Lisbon , Portugal. · g Department of Oncology , Royal Marsden Hospital , London & Surrey , UK. · h Department of Comprehensive Cancer Care , Masaryk Memorial Cancer Institute , Brno , Czech Republic. · i Queen Elizabeth Hospital and Lyell McEwin Hospital , Adelaide , Australia. ·Expert Rev Anticancer Ther · Pubmed #28817982.

ABSTRACT: INTRODUCTION: Despite recent progress, the outlook for most patients with pancreatic cancer remains poor. There is variation in how patients are managed globally due to differing interpretations of the evidence, partly because studies in this disease are challenging to undertake. This article collates the evidence upon which current best practice is based and offers an expert opinion from an international faculty on how latest developments should influence current treatment paradigms. Areas covered: Optimal chemotherapy for first and subsequent lines of therapy; optimal management of locally advanced, non-metastatic cancer including the role of neoadjuvant chemo(radio)therapy, current evidence for adjuvant chemotherapy, major advances in pancreatic cancer genomics and challenges in supportive care particularly relevant to patients with pancreatic cancer. For each section, literature was reviewed by comprehensive search techniques, including clinical trial websites and abstracts from international cancer meetings. Expert commentary: For each section, a commentary is provided. Overall the challenges identified were: difficulties in diagnosing pancreatic cancer early, challenges for performing randomised clinical trials in all stages of the disease, some progress in systemic therapy with new agents and in identifying molecular subtypes that may be clinically relevant and move towards personalized therapy, but still, pancreatic cancer remains a very poor prognosis cancer with significant palliative care needs.

3 Review Circulating pancreatic stellate (stromal) cells in pancreatic cancer-a fertile area for novel research. 2017

Pang, Tony C Y / Xu, Zhihong / Pothula, Srinivasa / Becker, Therese / Goldstein, David / Pirola, Romano C / Wilson, Jeremy S / Apte, Minoti V. ·Pancreatic Research Group, South Western Sydney Clinical School,University of New South Wales, and Ingham Institute of Applied Medical Research, Australia and. · Centre for Circulating Tumour Cell Diagnostics and Research, InghamInstitute for Applied Medical Research, South Western Sydney Clinical School, University of New South Wales, and School ofMedicine, Western Sydney University, Australia. ·Carcinogenesis · Pubmed #28379317.

ABSTRACT: Pancreatic stellate cells (PSCs) are known to play an important role in facilitating pancreatic cancer progression-both in terms of local tumour growth as well as the establishment of metastases. We have previously demonstrated that PSCs from the primary cancer seed to distant metastatic sites. We therefore hypothesise that PSCs circulate along with pancreatic cancer cells (circulating tumour cells-CTCs) to help create a growth permissive microenvironment at distant metastatic sites. This review aims to explore the concept of circulating PSCs in pancreatic cancer and suggests future directions for research in this area.

4 Review Rituximab to treat gemcitabine-induced hemolytic-uremic syndrome (HUS) in pancreatic adenocarcinoma: a case series and literature review. 2017

Ritchie, Georgia E / Fernando, Mangalee / Goldstein, David. ·Department of Medical Oncology and Renal Medicine, Prince of Wales Hospital, Barker St, Randwick, NSW, 2031, Australia. georgia.ritchie@sesiahs.health.nsw.gov.au. · Prince of Wales Clinical School, University of New South Wales Medical School, Kensington, Australia. georgia.ritchie@sesiahs.health.nsw.gov.au. · Department of Medical Oncology and Renal Medicine, Prince of Wales Hospital, Barker St, Randwick, NSW, 2031, Australia. · Prince of Wales Clinical School, University of New South Wales Medical School, Kensington, Australia. ·Cancer Chemother Pharmacol · Pubmed #27497971.

ABSTRACT: PURPOSE: Hemolytic-uremic syndrome (HUS) is a rare side effect of gemcitabine, which is reported as having a high morbidity and mortality despite interventions with standard HUS therapies including plasmapheresis. The purpose of this report was to describe the successful treatment of gemcitabine-induced HUS (G-HUS) with rituximab. It also aims to summarize the literature regarding the morbidity and mortality of G-HUS in pancreatic adenocarcinoma depending on the treatment given, ultimately providing some guidance for beneficial therapies. METHODS: This is a retrospective report of three patients with pancreatic adenocarcinoma who developed G-HUS and were treated with a combination of therapies including rituximab. RESULTS: All three patients received a combination of therapies to treat their HUS. One patient appeared to have some benefit with plasmapheresis. Resolution occurred following one course of rituximab for all three patients. This resolution has been long lasting with a minimum of eighteen month's follow-up. Similarly, in our literature review a variety of therapies were utilized, but immune therapies appear to reverse HUS if other therapies are failing. CONCLUSION: Rituximab can be an effective therapy for reversal of hemolysis and stabilization of renal function in G-HUS when other therapies fail.

5 Review Key role of pancreatic stellate cells in pancreatic cancer. 2016

Pothula, Srinivasa P / Xu, Zhihong / Goldstein, David / Pirola, Romano C / Wilson, Jeremy S / Apte, Minoti V. ·Pancreatic Research Group, South Western Sydney Clinical School, Faculty of Medicine, The University of New South Wales, Sydney, Australia; Ingham Institute for Applied Medical Research, Liverpool, NSW, Australia. · Pancreatic Research Group, South Western Sydney Clinical School, Faculty of Medicine, The University of New South Wales, Sydney, Australia. · Pancreatic Research Group, South Western Sydney Clinical School, Faculty of Medicine, The University of New South Wales, Sydney, Australia; Ingham Institute for Applied Medical Research, Liverpool, NSW, Australia. Electronic address: m.apte@unsw.edu.au. ·Cancer Lett · Pubmed #26571462.

ABSTRACT: Pancreatic stellate cells (PSCs) are responsible for producing the collagenous stroma in pancreatic cancer. Findings from the majority of in vitro and in vivo studies to date indicate that PSCs interact with cancer cells as well as with other cellular elements in the stroma including immune cells, endothelial cells and neuronal cells to set up a growth permissive microenvironment for pancreatic tumours. However, two recent studies reporting a protective effect of myofibroblasts in pancreatic cancer have served to remind researchers of the possibility that the role of PSCs in this disease may be context and time-dependent, such that any possible early protective role of PSCs is subverted in later stages by the ability of cancer cells to turn PSCs into cancer-promoting aides. This concept is supported by the development in recent years of several novel therapeutic approaches targeting the stroma that have been successfully applied in pre-clinical settings to inhibit disease progression. A multi-pronged approach aimed at tumour cells as well as stromal elements may be the key to achieving better clinical outcomes in patients with pancreatic cancer.

6 Review WITHDRAWN: Chemotherapy and radiotherapy for inoperable advanced pancreatic cancer. 2009

Yip, Desmond / Karapetis, Christos / Strickland, Andrew / Steer, Christopher B / Goldstein, David. ·Medical Oncology Unit, The Canberra Hospital, Yamba Drive, Garran, ACT, Australia, 2605. ·Cochrane Database Syst Rev · Pubmed #19821291.

ABSTRACT: BACKGROUND: Pancreatic cancer has a poor prognosis. The benefit of chemotherapy, radiotherapy or both as a palliative treatment of advanced or relapsed disease is uncertain. OBJECTIVES: To assess the effects of chemotherapy and/or radiotherapy in the management of pancreatic adenocarcinoma in people with inoperable advanced disease. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), which includes the Cochrane Upper Gastrointestinal and Pancreatic Diseases (UGPD) Group Trials Register (The Cochrane Library 2005, Issue 1); CANCERLIT (1975-2002); MEDLINE (1966 to January 2005); and EMBASE (1980 to January 2005). We handsearched reference lists from trials revealed by electronic searches to identify further relevant trials. We searched published abstracts from relevant conference proceedings. We contacted colleagues and experts in the field, and asked them to provide details of outstanding clinical trials and any relevant unpublished materials. SELECTION CRITERIA: Randomised controlled trials (single- or double-blind) in patients with advanced inoperable pancreatic cancer, in which one of the intervention types (chemotherapy or radiotherapy) was contrasted with either placebo or another type of intervention. Studies comparing non-chemotherapy agents such as biological agents, hormones, immunostimulants, vaccines and cytokines were excluded. DATA COLLECTION AND ANALYSIS: Studies were assessed for eligibility and quality. Data were extracted by groups of two independent reviewers, with conflicts resolved by a third reviewer. Study authors were contacted for more information. MAIN RESULTS: Fifty trials (7043 participants) were included. Chemotherapy significantly reduced the one-year mortality (odds ratio (OR) 0.37, 95% confidence interval (CI) 0.25 to 0.57, P value < 0.00001) when compared to best supportive care. Also, chemoradiation improved one year survival (0% versus 58%, P value 0.001) when compared to best supportive care. There was no significant difference in one-year mortality for 5FU alone versus 5FU combinations (OR 0.90, 95% CI 0.62 to 1.30); single-agent chemotherapy versus gemcitabine (OR 1.34, 95% CI 0.88 to 2.02, P value 0.17); or gemcitabine alone versus gemcitabine combinations (OR 0.88, 95% CI 0.74 to 1.05). However, subgroup analysis showed that platinum-gemcitabine combinations reduced six-month mortality compared to gemcitabine alone (OR 0.59, 95% CI 0.43 to 0.81, P value 0.001). A qualitative overview suggested that chemoradiation produced better survivals than either best supportive care or radiotherapy. Chemoradiation treatment was associated with more toxicity. AUTHORS' CONCLUSIONS: Chemotherapy appears to prolong survival in people with advanced pancreatic cancer and can confer clinical benefits and improve quality of life. Combination chemotherapy did not improve overall survival compared to single-agent chemotherapy. Gemcitabine is an acceptable control arm for future trials investigating scheduling and combinations with novel agents. There is insufficient evidence to recommend chemoradiation in patients with locally advanced inoperable pancreatic cancer as a superior alternative to chemotherapy alone.

7 Review Pancreatic stellate cells and pancreatic cancer cells: an unholy alliance. 2008

Vonlaufen, Alain / Phillips, Phoebe A / Xu, Zhihong / Goldstein, David / Pirola, Romano C / Wilson, Jeremy S / Apte, Minoti V. ·Pancreatic Research Group, South Western Sydney Clinical School and School of Medical Sciences/Pathology, The University of New South Wales and Sydney, Sydney, NSW, Australia. ·Cancer Res · Pubmed #18829522.

ABSTRACT: Pancreatic cancer--a tumor displaying a particularly abundant stromal reaction--is notorious for its poor prognosis. Recent studies, via newly developed orthotopic models, provide compelling evidence of an important role for pancreatic stellate cells (PSC) in pancreatic cancer progression. Characterization of the mechanisms mediating PSC-cancer interactions will lead to the development of much needed alternative therapeutic approaches to improve disease outcome.

8 Clinical Trial Tumor Reduction in Primary and Metastatic Pancreatic Cancer Lesions With nab-Paclitaxel and Gemcitabine: An Exploratory Analysis From a Phase 3 Study. 2017

Kunzmann, Volker / Ramanathan, Ramesh K / Goldstein, David / Liu, Helen / Ferrara, Stefano / Lu, Brian / Renschler, Markus F / Von Hoff, Daniel D. ·From the *Medizinische Klinik und Poliklinik II, University of Würzburg, Würzburg, Germany; †Mayo Clinic, Scottsdale, AZ; ‡Prince of Wales Hospital, Sydney, New South Wales, Australia; §Celgene Corporation, Summit, NJ; and ∥Translational German Research Institute and Honor Health Research Institute, Scottsdale, AZ. ·Pancreas · Pubmed #27841795.

ABSTRACT: OBJECTIVES: Results from the phase 3 Metastatic Pancreatic Adenocarcinoma Clinical Trial (MPACT) led to approval of nab-paclitaxel plus gemcitabine for first-line treatment of metastatic pancreatic cancer. The current analysis evaluated the effects of nab-paclitaxel plus gemcitabine versus gemcitabine on primary pancreatic and metastatic lesions. METHODS: In this analysis of the previously described MPACT trial, changes in pancreatic and metastatic tumor burden were assessed using independently measured diameters of lesions on computed tomography or magnetic resonance imaging scans. Changes in the sums of longest tumor diameters were summarized using descriptive statistics and were included in a multivariate analysis of overall survival. RESULTS: Primary pancreatic lesion measurement was feasible. Reductions in primary pancreatic tumor burden and metastatic burden from baseline to nadir were significantly greater with nab-paclitaxel plus gemcitabine versus gemcitabine. Baseline pancreatic tumor burden was independently predictive of survival. Both regimens elicited linear reductions in primary pancreatic and metastatic tumor burden through time. There was a high within-patient concordance of tumor changes between primary pancreatic lesions and metastatic lesions. CONCLUSIONS: This analysis of MPACT demonstrated significant tumor shrinkage benefit for nab-paclitaxel plus gemcitabine in both primary pancreatic and metastatic lesions, supporting ongoing evaluation of this regimen in locally advanced disease.

9 Clinical Trial Prognostic nomogram and score to predict overall survival in locally advanced untreated pancreatic cancer (PROLAP). 2016

Vernerey, Dewi / Huguet, Florence / Vienot, Angélique / Goldstein, David / Paget-Bailly, Sophie / Van Laethem, Jean-Luc / Glimelius, Bengt / Artru, Pascal / Moore, Malcolm J / André, Thierry / Mineur, Laurent / Chibaudel, Benoist / Benetkiewicz, Magdalena / Louvet, Christophe / Hammel, Pascal / Bonnetain, Franck. ·Methodological and Quality of Life in Oncology Unit, EA 3181, University Hospital of Besançon, 3 Boulevard Alexandre Fleming, Besançon 25030, France. · Oncology Multidisciplinary Research Group (GERCOR), 151 rue du Faubourg Saint Antoine, Paris 75011, France. · Department of Radiotherapy, Tenon Hospital (AP-HP), 4 rue de la Chine, Paris 75020, France. · Department of Gastroenterology, University Hospital of Besançon, 3 Boulevard Alexandre Fleming, Besançon 25030, France. · Department of Medical Oncology, Prince of Wales hospital and Prince of Wales Clinical school, UNSW, Sydney, New South Wales 2031, Australia. · AGITG (Australasian Gastrointestinal Trials Group), 119-143 Missenden Rd, Camperdown, New South Wales 2050, Australia. · Department of Gastroenterology, Erasme University Hospital, Route de Lennik 808, Brussels 1070, Belgium. · Department of Radiology, Oncology and Radiation Science, University of Uppsala, Uppsala 75105, Sweden. · Department of Gastroenterology, Jean Mermoz Hospital, 55 avenue Mermoz, Lyon 69008, France. · Department of Medical Oncology, Princess Margaret Hospital, 610 University Avenue, Toronto, Ontario M5G 2M9, Canada. · Department of Medical Oncology, Saint-Antoine Hospital (AP-HP), 184 rue du Faubourg Saint Antoine, Paris 75011, France. · Department of Radiotherapy and Medical Oncology, Sainte-Catherine Institute, 250 Chemin de Baigne Pieds, Avignon 84918, France. · Department of Medical Oncology, Franco-British Hospital Institute, 3 Rue Barbès, Levallois-Perret 92300, France. · Department of Medical Oncology, Institute Mutualiste Montsouris, 42 Boulevard Jourdan, Paris 75014, France. · Department of Digestive Oncology, Beaujon Hospital (AP-HP), 100 boulevard du General Leclerc, Clichy 92110, France. ·Br J Cancer · Pubmed #27404456.

ABSTRACT: BACKGROUND: The management of locally advanced pancreatic cancer (LAPC) patients remains controversial. Better discrimination for overall survival (OS) at diagnosis is needed. We address this issue by developing and validating a prognostic nomogram and a score for OS in LAPC (PROLAP). METHODS: Analyses were derived from 442 LAPC patients enrolled in the LAP07 trial. The prognostic ability of 30 baseline parameters was evaluated using univariate and multivariate Cox regression analyses. Performance assessment and internal validation of the final model were done with Harrell's C-index, calibration plot and bootstrap sample procedures. On the basis of the final model, a prognostic nomogram and a score were developed, and externally validated in 106 consecutive LAPC patients treated in Besançon Hospital, France. RESULTS: Age, pain, tumour size, albumin and CA 19-9 were independent prognostic factors for OS. The final model had good calibration, acceptable discrimination (C-index=0.60) and robust internal validity. The PROLAP score has the potential to delineate three different prognosis groups with median OS of 15.4, 11.7 and 8.5 months (log-rank P<0.0001). The score ability to discriminate OS was externally confirmed in 63 (59%) patients with complete clinical data derived from a data set of 106 consecutive LAPC patients; median OS of 18.3, 14.1 and 7.6 months for the three groups (log-rank P<0.0001). CONCLUSIONS: The PROLAP nomogram and score can accurately predict OS before initiation of induction chemotherapy in LAPC-untreated patients. They may help to optimise clinical trials design and might offer the opportunity to define risk-adapted strategies for LAPC management in the future.

10 Clinical Trial Second-line therapy after nab-paclitaxel plus gemcitabine or after gemcitabine for patients with metastatic pancreatic cancer. 2016

Chiorean, E Gabriela / Von Hoff, Daniel D / Tabernero, Josep / El-Maraghi, Robert / Ma, Wen Wee / Reni, Michele / Harris, Marion / Whorf, Robert / Liu, Helen / Li, Jack Shiansong / Manax, Victoria / Romano, Alfredo / Lu, Brian / Goldstein, David. ·Division Oncology, Department of Medicine, University of Washington, 825 Eastlake Avenue E, G4-833, Seattle, WA 98109-1023, USA. · Translational Genomics Research Institute and HonorHealth, 445 North Fifth Street, Suite 600, Phoenix, AZ 85004, USA. · Vall d'Hebron Institute of Oncology (VHIO), P Vall d'Hebron 119-129, Barcelona 08035, Spain. · Royal Victoria Hospital Barrie Canada, 201 Georgian Drive, Barrie, Ontario, Canada L4M 6M2. · Roswell Park Cancer Institute, 665 Elm Street, Buffalo, NY 14203, USA. · San Raffaele Scientific Institute, Via Olgetina 60, 20132 Milan, Italy. · Monash Health, 246 Clayton Road, Melbourne VIC 3168, Australia. · Florida Cancer Specialists, 2401 60th Street Ct W, Bradenton, FL 34209-5500, USA. · Celgene Corporation, 86 Morris Avenue, Summit, NJ 07901, USA. · Department of Medical Oncology, Prince of Wales Hospital, South Sydney Illawarra, Barker Street, Sydney NSW 2031, Australia. ·Br J Cancer · Pubmed #27351217.

ABSTRACT: BACKGROUND: This exploratory analysis evaluated second-line (2L) therapy for metastatic pancreatic cancer in a large phase 3 trial (MPACT). METHODS: Patients who received first-line (1L) nab-paclitaxel+gemcitabine (nab-P+Gem) or Gem were assessed for survival based on 2L treatment received. Multivariate analyses tested influence of treatment effect and prognostic factors on survival. RESULTS: The majority of 2L treatments (267 out of 347, 77%) contained a fluoropyrimidine (5-fluorouracil or capecitabine). Median total survival (1L randomisation to death) for patients who received 2L treatment after 1L nab-P+Gem vs Gem alone was 12.8 vs 9.9 months (P=0.015). Median total survival for patients with a fluoropyrimidine-containing 2L therapy after nab-P+Gem vs Gem was 13.5 vs 9.5 months (P=0.012). Median 2L survival (duration from start of 2L therapy to death) was 5.3 vs 4.5 months for nab-P+Gem vs Gem, respectively (P=0.886). Factors significantly associated with longer post-1L survival by multivariate analyses included 1L nab-P+Gem, receiving 2L treatment, longer 1L progression-free survival, and Karnofsky performance status⩾70 and neutrophil-to-lymphocyte ratio⩽5 at the end of 1L treatment. CONCLUSIONS: These findings support the use of 2L therapy for patients with metastatic pancreatic cancer. Fluoropyrimidine-containing treatment after 1L nab-P+Gem is an active regimen with significant clinical effect.

11 Clinical Trial Effect of Chemoradiotherapy vs Chemotherapy on Survival in Patients With Locally Advanced Pancreatic Cancer Controlled After 4 Months of Gemcitabine With or Without Erlotinib: The LAP07 Randomized Clinical Trial. 2016

Hammel, Pascal / Huguet, Florence / van Laethem, Jean-Luc / Goldstein, David / Glimelius, Bengt / Artru, Pascal / Borbath, Ivan / Bouché, Olivier / Shannon, Jenny / André, Thierry / Mineur, Laurent / Chibaudel, Benoist / Bonnetain, Franck / Louvet, Christophe / Anonymous6180866. ·Department of Digestive Oncology, Beaujon Hospital (AP-HP), Clichy, France. · Department of Radiotherapy, Tenon Hospital (AP-HP), Paris, France. · Department of Gastroenterology, Erasme University Hospital, Brussels, Belgium. · Department of Medical Oncology, Prince of Wales Hospital, Sydney, Australia5Australasian Gastrointestinal Trials Group (AGITG), Camperdown, Australia6Prince of Wales Clinical School, University of New South Wales, Sydney, Australia. · Department of Radiology, Oncology, and Radiation Science, University of Uppsala, Uppsala, Sweden. · Department of Gastroenterology, Jean Mermoz Hospital, Lyon, France. · Department of Gastroenterology, Saint-Luc University Clinics, Brussels, Belgium. · Department of Gastroenterology, Robert Debré Hospital, Reims, France. · Australasian Gastrointestinal Trials Group (AGITG), Camperdown, Australia6Prince of Wales Clinical School, University of New South Wales, Sydney, Australia11Department of Medical Oncology, Nepean Hospital NSW, Sydney, Australia. · Department of Medical Oncology, Saint-Antoine Hospital (AP-HP), Paris, France. · Department of Radiotherapy and Medical Oncology, Sainte-Catherine Institute, Avignon, France. · Department of Medical Oncology, Franco-British Hospital Institute, Levallois-Perret, France15Oncology Multidisciplinary Research Group (GERCOR), Paris, France. · Department of Methodology and Quality of Life in Oncology, Hospital Minjoz, Besançon, France. · Department of Medical Oncology, Institute Mutualiste Montsouris, Paris, France. ·JAMA · Pubmed #27139057.

ABSTRACT: IMPORTANCE: In locally advanced pancreatic cancer, the role of chemoradiotherapy is controversial and the efficacy of erlotinib is unknown. OBJECTIVES: To assess whether chemoradiotherapy improves overall survival of patients with locally advanced pancreatic cancer controlled after 4 months of gemcitabine-based induction chemotherapy and to assess the effect of erlotinib on survival. DESIGN, SETTING, AND PARTICIPANTS: In LAP07, an international, open-label, phase 3 randomized trial, 449 patients were enrolled between 2008 and 2011. Follow-up ended in February 2013. INTERVENTIONS: In the first randomization, 223 patients received 1000 mg/m2 weekly of gemcitabine alone and 219 patients received 1000 mg/m2 of gemcitabine plus 100 mg/d of erlotinib. In the second randomization involving patients with progression-free disease after 4 months, 136 patients received 2 months of the same chemotherapy and 133 underwent chemoradiotherapy (54 Gy plus capecitabine). MAIN OUTCOMES AND MEASURES: The primary outcome was overall survival from the date of the first randomization. Secondary outcomes were the effect of erlotinib and quality assurance of radiotherapy on overall survival, progression-free survival of gemcitabine-erlotinib and erlotinib maintenance with gemcitabine alone at the second randomization, and toxic effects. RESULTS: A total of 442 of the 449 patients (232 men; median age, 63.3 years) enrolled underwent the first randomization. Of these, 269 underwent the second randomization. Interim analysis was performed when 221 patients died (109 in the chemoradiotherapy group and 112 in the chemotherapy group), reaching the early stopping boundaries for futility. With a median follow-up of 36.7 months, the median overall survival from the date of the first randomization was not significantly different between chemotherapy at 16.5 months (95% CI, 14.5-18.5 months) and chemoradiotherapy at 15.2 months (95% CI, 13.9-17.3 months; hazard ratio [HR], 1.03; 95% CI, 0.79-1.34; P = .83). Median overall survival from the date of the first randomization for the 223 patients receiving gemcitabine was 13.6 months (95% CI, 12.3-15.3 months) and was 11.9 months (95% CI, 10.4-13.5 months) for the 219 patients receiving gemcitabine plus erlotinib (HR, 1.19; 95% CI, 0.97-1.45; P = .09; 188 deaths vs 191 deaths). Chemoradiotherapy was associated with decreased local progression (32% vs 46%, P = .03) and no increase in grade 3 to 4 toxicity, except for nausea. CONCLUSIONS AND RELEVANCE: In this open-label, randomized trial involving patients with locally advanced pancreatic cancer with disease controlled after 4 months of induction chemotherapy, there was no significant difference in overall survival with chemoradiotherapy compared with chemotherapy alone and there was no significant difference in overall survival with gemcitabine compared with gemcitabine plus erlotinib used as maintenance therapy. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00634725.

12 Clinical Trial Development of peripheral neuropathy and its association with survival during treatment with nab-paclitaxel plus gemcitabine for patients with metastatic adenocarcinoma of the pancreas: A subset analysis from a randomised phase III trial (MPACT). 2016

Goldstein, David / Von Hoff, Daniel D / Moore, Malcolm / Greeno, Edward / Tortora, Giampaolo / Ramanathan, Ramesh K / Macarulla, Teresa / Liu, Helen / Pilot, Richard / Ferrara, Stefano / Lu, Brian. ·Prince of Wales Hospital, Department of Oncology, South Eastern Sydney Illawarra, NSW Health, Barker Street, Randwick, NSW 2031, Australia; University of New South Wales, Australia. Electronic address: david.goldstein@sesiahs.health.nsw.gov.au. · Scottsdale Healthcare/TGen, Bisgrove Research Pavilion, 10510 North 92nd Street, Suite 200, Scottsdale, AZ 85258, USA. · Princess Margaret Hospital, 5th Floor 708, 610 University Avenue, Toronto, Ontario M5G2M9, Canada. · University of Minnesota, Division of Hematology, Oncology and Transplantation, 420 Delaware Street SE, MMC 480, Minneapolis, MN 55455, USA. · Azienda Ospedaliera Universitaria Integrata di Verona, Policlinico Borgo Roma, Piazzale L. Scuro, 10, 37134 Verona, Italy. · Mayo Clinic, 13400 E Shea Blvd FL 3, Scottsdale, AZ 85259, USA. · Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology (VHIO), P. Vall d'Hebron 119-129, Barcelona, Spain. · Celgene Corporation, 86 Morris Avenue, Summit, NJ 07901, USA. ·Eur J Cancer · Pubmed #26655559.

ABSTRACT: BACKGROUND: In a phase III trial in patients with metastatic pancreatic cancer (MPC), nab-paclitaxel plus gemcitabine (nab-P/Gem) demonstrated greater efficacy but higher rates of peripheral neuropathy (PN) versus Gem. This exploratory analysis aimed to characterise the frequency, duration, and severity of PN with nab-P/Gem in the MPACT study. PATIENTS AND METHODS: Patients with previously untreated MPC received nab-P/Gem or Gem. PN was evaluated using a broad-spectrum group of Standardised Medical Dictionary for Regulatory Activities Queries (SMQ) and graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.0. A case report form was completed by physicians on day 1 of each cycle (also graded by NCI CTCAE version 3.0). RESULTS: In the nab-P/Gem arm, 227/421 patients (54%) experienced any-grade PN and 70 (17%) experienced grade III PN. No grade IV PN was reported. Most early-onset PN events were grade I, and treatment-related grade III PN occurred in 7% of patients who received up to three cycles of nab-P. Of those who developed grade III PN with nab-P/Gem treatment, 30 (43%) improved to grade ≤ I (median time to improvement = 29 days) and 31 (44%) resumed therapy. Development of PN was associated with efficacy; median overall survival in patients with grade III versus 0 PN was 14.9 versus 5.9 months (hazard ratio, 0.33; P < .0001). CONCLUSIONS: nab-P/Gem was associated with grade III PN in a small percentage of patients. PN development was associated with longer treatment duration and improved survival. Grade III PN was reversible to grade ≤ I in many patients (median ≈ 1 month) NCT00844649.

13 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.

14 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.

15 Clinical Trial Optimal duration and timing of adjuvant chemotherapy after definitive surgery for ductal adenocarcinoma of the pancreas: ongoing lessons from the ESPAC-3 study. 2014

Valle, Juan W / Palmer, Daniel / Jackson, Richard / Cox, Trevor / Neoptolemos, John P / Ghaneh, Paula / Rawcliffe, Charlotte L / Bassi, Claudio / Stocken, Deborah D / Cunningham, David / O'Reilly, Derek / Goldstein, David / Robinson, Bridget A / Karapetis, Christos / Scarfe, Andrew / Lacaine, Francois / Sand, Juhani / Izbicki, Jakob R / Mayerle, Julia / Dervenis, Christos / Oláh, Attila / Butturini, Giovanni / Lind, Pehr A / Middleton, Mark R / Anthoney, Alan / Sumpter, Kate / Carter, Ross / Büchler, Markus W. ·Juan W. Valle, Derek O'Reilly, Manchester Academic Health Sciences Centre, Christie Hospital NHS Foundation Trust and University of Manchester, Manchester · Richard Jackson, Trevor Cox, John P. Neoptolemos, Paula Ghaneh, Charlotte L. Rawcliffe, Liverpool Cancer Research UK Centre and the National Institute for Health Research Pancreas Biomedical Research Unit, University of Liverpool, Liverpool · Daniel Palmer, the Queen Elizabeth Hospital, University Hospital Birmingham NHS Foundation Trust · Deborah D. Stocken, the Cancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham · David Cunningham, Royal Marsden Hospital Foundation Trust, Sutton · Mark R. Middleton, Churchill Hospital, Oxford University Hospitals NHS Trust, Oxford · Alan Anthoney, The Leeds Teaching Hospital Trust, Leeds · Kate Sumpter, Freeman Hospital, Newcastle upon Tyne · Ross Carter, Glasgow Royal Infirmary, Glasgow, United Kingdom · Claudio Bassi, Giovanni Butturini, University of Verona, Verona, Italy · David Goldstein, Bridget A. Robinson, Christos Karapetis, the Australasian Gastro-Intestinal Trials Group, Camperdown, Australia · Andrew Scarfe, University of Alberta, Edmonton, Canada · Francois Lacaine, Hôpital TENON, Assistance Publique Hôpitaux de Paris, Universite Pierre Et Marie Curie, Paris, France · Juhani Sand, Tampere University Hospital, Tampere, Finland · Jakob R. Izbicki, University of Hamburg, Hamburg · Julia Mayerle, Ernst-Moritz-Arndt-Universität Greifswald, Greifswald · Markus W. Büchler, University of Heidelberg, Heidelberg, Germany · Christos Dervenis, the Agia Olga Hospital, Athens, Greece · Attila Oláh, the Petz Aladar Hospital, Gyor, Hungary · Pehr A. Lind, Karolinska-Stockholm Söder Hospital, Stockholm, Sweden. ·J Clin Oncol · Pubmed #24419109.

ABSTRACT: PURPOSE: Adjuvant chemotherapy improves patient survival rates after resection for pancreatic adenocarcinoma, but the optimal duration and time to initiate chemotherapy is unknown. PATIENTS AND METHODS: Patients with pancreatic ductal adenocarcinoma treated within the international, phase III, European Study Group for Pancreatic Cancer-3 (version 2) study were included if they had been randomly assigned to chemotherapy. Overall survival analysis was performed on an intention-to-treat basis, retaining patients in their randomized groups, and adjusting the overall treatment effect by known prognostic variables as well as the start time of chemotherapy. RESULTS: There were 985 patients, of whom 486 (49%) received gemcitabine and 499 (51%) received fluorouracil; 675 patients (68%) completed all six cycles of chemotherapy (full course) and 293 patients (30%) completed one to five cycles. Lymph node involvement, resection margins status, tumor differentiation, and completion of therapy were all shown by multivariable Cox regression to be independent survival factors. Overall survival favored patients who completed the full six courses of treatment versus those who did not (hazard ratio [HR], 0.516; 95% CI, 0.443 to 0.601; P < .001). Time to starting chemotherapy did not influence overall survival rates for the full study population (HR, 0.985; 95% CI, 0.956 to 1.015). Chemotherapy start time was an important survival factor only for the subgroup of patients who did not complete therapy, in favor of later treatment (P < .001). CONCLUSION: Completion of all six cycles of planned adjuvant chemotherapy rather than early initiation was an independent prognostic factor after resection for pancreatic adenocarcinoma. There seems to be no difference in outcome if chemotherapy is delayed up to 12 weeks, thus allowing adequate time for postoperative recovery.

16 Clinical Trial Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. 2013

Von Hoff, Daniel D / Ervin, Thomas / Arena, Francis P / Chiorean, E Gabriela / Infante, Jeffrey / Moore, Malcolm / Seay, Thomas / Tjulandin, Sergei A / Ma, Wen Wee / Saleh, Mansoor N / Harris, Marion / Reni, Michele / Dowden, Scot / Laheru, Daniel / Bahary, Nathan / Ramanathan, Ramesh K / Tabernero, Josep / Hidalgo, Manuel / Goldstein, David / Van Cutsem, Eric / Wei, Xinyu / Iglesias, Jose / Renschler, Markus F. ·From the Translational Genomics Research Institute, Phoenix, and Virginia G. Piper Cancer Center, Scottsdale - both in Arizona (D.D.V.H., R.K.R.) · Cancer Specialists, Fort Myers, FL (T.E.) · Arena Oncology Associates, Lake Success (F.P.A.), and Roswell Park Cancer Institute, Buffalo (W.W.M.) - both in New York · University of Washington, Seattle (E.G.C.) · Sarah Cannon Research Institute-Tennessee Oncology, Nashville (J. Infante) · Princess Margaret Hospital, Toronto (M.M.) · Atlanta Cancer Care (T.S.) and Georgia Cancer Specialists (M.N.S.) - both in Atlanta · Blokhin Cancer Research Center, Moscow (S.A.T.) · Southern Health, East Bentleigh, VIC (M.H.), Prince of Wales Hospital, Sydney (D.G.), and Bionomics, Thebarton, SA (J. Iglesias) - all in Australia · San Raffaele Scientific Institute, Milan (M.R.) · Tom Baker Cancer Centre, Calgary, AB, Canada (S.D.) · Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (D.L.) · University of Pittsburgh Medical Center, Pittsburgh (N.B.) · Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona (J.T.) · Centro Integral Oncológico Clara Campal, Madrid (M.H.) · University Hospitals Leuven and Katholieke Universiteit Leuven, Leuven, Belgium (E.V.C.) · and Celgene, Summit, NJ (X.W., M.F.R.). ·N Engl J Med · Pubmed #24131140.

ABSTRACT: BACKGROUND: In a phase 1-2 trial of albumin-bound paclitaxel (nab-paclitaxel) plus gemcitabine, substantial clinical activity was noted in patients with advanced pancreatic cancer. We conducted a phase 3 study of the efficacy and safety of the combination versus gemcitabine monotherapy in patients with metastatic pancreatic cancer. METHODS: We randomly assigned patients with a Karnofsky performance-status score of 70 or more (on a scale from 0 to 100, with higher scores indicating better performance status) to nab-paclitaxel (125 mg per square meter of body-surface area) followed by gemcitabine (1000 mg per square meter) on days 1, 8, and 15 every 4 weeks or gemcitabine monotherapy (1000 mg per square meter) weekly for 7 of 8 weeks (cycle 1) and then on days 1, 8, and 15 every 4 weeks (cycle 2 and subsequent cycles). Patients received the study treatment until disease progression. The primary end point was overall survival; secondary end points were progression-free survival and overall response rate. RESULTS: A total of 861 patients were randomly assigned to nab-paclitaxel plus gemcitabine (431 patients) or gemcitabine (430). The median overall survival was 8.5 months in the nab-paclitaxel-gemcitabine group as compared with 6.7 months in the gemcitabine group (hazard ratio for death, 0.72; 95% confidence interval [CI], 0.62 to 0.83; P<0.001). The survival rate was 35% in the nab-paclitaxel-gemcitabine group versus 22% in the gemcitabine group at 1 year, and 9% versus 4% at 2 years. The median progression-free survival was 5.5 months in the nab-paclitaxel-gemcitabine group, as compared with 3.7 months in the gemcitabine group (hazard ratio for disease progression or death, 0.69; 95% CI, 0.58 to 0.82; P<0.001); the response rate according to independent review was 23% versus 7% in the two groups (P<0.001). The most common adverse events of grade 3 or higher were neutropenia (38% in the nab-paclitaxel-gemcitabine group vs. 27% in the gemcitabine group), fatigue (17% vs. 7%), and neuropathy (17% vs. 1%). Febrile neutropenia occurred in 3% versus 1% of the patients in the two groups. In the nab-paclitaxel-gemcitabine group, neuropathy of grade 3 or higher improved to grade 1 or lower in a median of 29 days. CONCLUSIONS: In patients with metastatic pancreatic adenocarcinoma, nab-paclitaxel plus gemcitabine significantly improved overall survival, progression-free survival, and response rate, but rates of peripheral neuropathy and myelosuppression were increased. (Funded by Celgene; ClinicalTrials.gov number, NCT00844649.).

17 Clinical Trial Impact of gemcitabine chemotherapy and 3-dimensional conformal radiation therapy/5-fluorouracil on quality of life of patients managed for pancreatic cancer. 2013

Short, Michala / Goldstein, David / Halkett, Georgia / Reece, William / Borg, Martin / Zissiadis, Yvonne / Kneebone, Andrew / Spry, Nigel. ·Discipline of Medical Radiation Sciences, University of Sydney, and Department of Medical Oncology, Prince of Wales Hospital, Sydney, New South Wales, Australia. ·Int J Radiat Oncol Biol Phys · Pubmed #22543205.

ABSTRACT: PURPOSE: To report quality of life (QOL) results for patients receiving chemoradiation therapy for pancreatic cancer. METHODS AND MATERIALS: Eligible patients (n=41 locally advanced, n=22 postsurgery) entered the B9E-AY-S168 study and received 1 cycle of induction gemcitabine (1000 mg/m2 weekly ×3 with 1-week break) followed by 3-dimensional conformal radiation therapy (RT) (54 Gy locally advanced and 45 Gy postsurgery) and concomitant continuous-infusion 5-fluorouracil (5FU) (200 mg/m2/d throughout RT). After 4 weeks, patients received an additional 3 cycles of consolidation gemcitabine chemotherapy. Patients completed the European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-PAN26 questionnaires at baseline, before RT/5FU, at end of RT/5FU, before consolidation gemcitabine, and at treatment completion. RESULTS: The patterns of change in global QOL scores differed between groups. In the locally advanced group global QOL scores were +13, +8, +3, and +1 compared with baseline before RT/5FU (P=.008), at end of RT/5FU, before consolidation gemcitabine, and at treatment completion, respectively. In the postsurgery group, global QOL scores were -3, +4, +15, and +17 compared with baseline at the same time points, with a significant improvement in global QOL before consolidation gemcitabine (P=.03). No significant declines in global QOL were reported by either cohort. CONCLUSIONS: This study demonstrates that global QOL and associated function and symptom profiles for pancreatic chemoradiation therapy differ between locally advanced and postsurgery patients, likely owing to differences in underlying disease status. For both groups, the treatment protocol was well tolerated and did not have a negative impact on patients' global QOL.

18 Clinical Trial Adjuvant chemotherapy with fluorouracil plus folinic acid vs gemcitabine following pancreatic cancer resection: a randomized controlled trial. 2010

Neoptolemos, John P / Stocken, Deborah D / Bassi, Claudio / Ghaneh, Paula / Cunningham, David / Goldstein, David / Padbury, Robert / Moore, Malcolm J / Gallinger, Steven / Mariette, Christophe / Wente, Moritz N / Izbicki, Jakob R / Friess, Helmut / Lerch, Markus M / Dervenis, Christos / Oláh, Attila / Butturini, Giovanni / Doi, Ryuichiro / Lind, Pehr A / Smith, David / Valle, Juan W / Palmer, Daniel H / Buckels, John A / Thompson, Joyce / McKay, Colin J / Rawcliffe, Charlotte L / Büchler, Markus W / Anonymous9620671. ·Liverpool Cancer Research UK Cancer Trials Unit, Cancer Research UK Centre, University of Liverpool, Fifth Floor, UCD Bldg, Daulby Street, Liverpool, L69 3GA, United Kingdom. j.p.neoptolemos@liverpool.ac.uk ·JAMA · Pubmed #20823433.

ABSTRACT: CONTEXT: Adjuvant fluorouracil has been shown to be of benefit for patients with resected pancreatic cancer. Gemcitabine is known to be the most effective agent in advanced disease as well as an effective agent in patients with resected pancreatic cancer. OBJECTIVE: To determine whether fluorouracil or gemcitabine is superior in terms of overall survival as adjuvant treatment following resection of pancreatic cancer. DESIGN, SETTING, AND PATIENTS: The European Study Group for Pancreatic Cancer (ESPAC)-3 trial, an open-label, phase 3, randomized controlled trial conducted in 159 pancreatic cancer centers in Europe, Australasia, Japan, and Canada. Included in ESPAC-3 version 2 were 1088 patients with pancreatic ductal adenocarcinoma who had undergone cancer resection; patients were randomized between July 2000 and January 2007 and underwent at least 2 years of follow-up. INTERVENTIONS: Patients received either fluorouracil plus folinic acid (folinic acid, 20 mg/m(2), intravenous bolus injection, followed by fluorouracil, 425 mg/m(2) intravenous bolus injection given 1-5 days every 28 days) (n = 551) or gemcitabine (1000 mg/m(2) intravenous infusion once a week for 3 of every 4 weeks) (n = 537) for 6 months. MAIN OUTCOME MEASURES: Primary outcome measure was overall survival; secondary measures were toxicity, progression-free survival, and quality of life. RESULTS: Final analysis was carried out on an intention-to-treat basis after a median of 34.2 (interquartile range, 27.1-43.4) months' follow-up after 753 deaths (69%). Median survival was 23.0 (95% confidence interval [CI], 21.1-25.0) months for patients treated with fluorouracil plus folinic acid and 23.6 (95% CI, 21.4-26.4) months for those treated with gemcitabine (chi(1)(2) = 0.7; P = .39; hazard ratio, 0.94 [95% CI, 0.81-1.08]). Seventy-seven patients (14%) receiving fluorouracil plus folinic acid had 97 treatment-related serious adverse events, compared with 40 patients (7.5%) receiving gemcitabine, who had 52 events (P < .001). There were no significant differences in either progression-free survival or global quality-of-life scores between the treatment groups. CONCLUSION: Compared with the use of fluorouracil plus folinic acid, gemcitabine did not result in improved overall survival in patients with completely resected pancreatic cancer. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00058201.

19 Clinical Trial 3D radiotherapy can be safely combined with sandwich systemic gemcitabine chemotherapy in the management of pancreatic cancer: factors influencing outcome. 2008

Spry, Nigel / Harvey, Jennifer / Macleod, Craig / Borg, Martin / Ngan, Samuel Y / Millar, Jeremy L / Graham, Peter / Zissiadis, Yvonne / Kneebone, Andrew / Carroll, Susan / Davies, Terri / Reece, William H H / Iacopetta, Barry / Goldstein, David. ·Department of Radiation Oncology, Sir Charles Gairdner Hospital, Nedlands, WA, Australia. Nigel.Spry@health.wa.gov.au ·Int J Radiat Oncol Biol Phys · Pubmed #18164859.

ABSTRACT: PURPOSE: The aim of this Phase II study was to examine whether concurrent continuous infusion 5-fluorouracil (CI 5FU) plus three-dimensional conformal planning radiotherapy sandwiched between gemcitabine chemotherapy is effective, tolerable, and safe in the management of pancreatic cancer. METHODS AND MATERIALS: Patients were enrolled in two strata: (1) resected pancreatic cancer at high risk of local relapse (postsurgery arm, n = 22) or (2) inoperable pancreatic cancer in head or body without metastases (locally advanced arm, n = 41). Gemcitabine was given at 1,000 mg/m(2) weekly for 3 weeks followed by 1 week rest then 5-6 weeks of radiotherapy and concurrent CI 5FU (200 mg/m(2)/day). After 4 weeks' rest, gemcitabine treatment was reinitiated for 12 weeks. RESULTS: For the two arms combined, treatment-related Grade 3 and 4 toxicities were reported by 25 (39.7%) and 7 (11.1%) patients, respectively. No significant late renal or hepatic toxicity was observed. In the postsurgery arm (R1 54.5%), median time to progressive disease from surgery was 11.0 months, median time to failure of local control was 32.9 months, and median survival time was 15.6 months. The 1- and 2-year survival rates were 63.6% and 31.8%. No significant associations between outcome and mutations in K-ras or TP53 or microsatellite instability were identified. Post hoc investigation of cancer antigen 19-9 levels found baseline levels and increases postbaseline were associated with shorter survival (p = 0.0061 and p < 0.0001, respectively). CONCLUSIONS: This three-dimensional chemoradiotherapy regimen is safe and promising, with encouraging local control for a substantial proportion of patients, and merits testing in a randomized trial.

20 Article Biliary Stenting in Patients With Pancreatic Cancer: Results From a Population-Based Cohort Study. 2018

Payne, Madeleine / Burmeister, Elizabeth A / Waterhouse, Mary / Jordan, Susan J / OʼConnell, Dianne L / Merrett, Neil D / Goldstein, David / Wyld, David / Beesley, Vanessa L / Gooden, Helen / Janda, Monika / Neale, Rachel E. · ·Pancreas · Pubmed #29215539.

ABSTRACT: OBJECTIVE: We aimed to describe management of biliary obstruction (BO) in the context of pancreatic cancer within a population-based cohort. METHODS: We examined management of BO in 1863 patients diagnosed as having pancreatic cancer in 2010/2011. We used descriptive statistics and logistic regression to describe patterns of biliary stent usage, complications and duration of patency, associations between preoperative stenting and surgical outcomes, and between patient factors and management of jaundice. RESULTS: Almost half of the people in the cohort (n = 909) were jaundiced within 12 months of diagnosis. Two-thirds of these had at least 1 stent inserted. Preoperative stenting, mostly with plastic stents, occurred for 72% of patients who experienced jaundice prior to an attempted resection but was not associated with surgical outcomes. Seventy percent of the jaundiced patients who did not have an attempted resection were stented. Metal stents were less frequently replaced within 30 days than plastic (9% vs 42%). Living in a rural area was associated with reduced likelihood of having jaundice managed. CONCLUSIONS: Plastic stents were still used frequently, despite guidelines recommending metal in most contexts. Patients living in rural areas were less likely to have BO managed. This work highlights the need to monitor current practice.

21 Article Association between pancreatic cancer patients' perception of their care coordination and patient-reported and survival outcomes. 2018

Beesley, Vanessa L / Janda, Monika / Burmeister, Elizabeth A / Goldstein, David / Gooden, Helen / Merrett, Neil D / O'Connell, Dianne L / Wyld, David K / Chan, Raymond J / Young, Jane M / Neale, Rachel E. ·Population Health Department,QIMR Berghofer Medical Research Institute,Brisbane,Queensland,Australia. · School of Public Health and Social Work,Queensland University of Technology,Brisbane,Queensland,Australia. · Department of Medical Oncology,Prince of Wales Hospital,Sydney,New South Wales,Australia. · Cancer Nursing Research Unit, University of Sydney,New South Wales,Sydney,Australia. · Discipline of Surgery,Western Sydney University,Sydney,New South Wales,Australia. · Cancer Research Division,Cancer Council of New South Wales,Sydney,New South Wales,Australia. · Department of Medical Oncology and Cancer Care Services,Royal Brisbane and Women's Hospital,Brisbane,Queensland,Australia. · RPA Institute of Academic Surgery and Surgical Outcomes Research Centre,Sydney Local Health District,Sydney,New South Wales,Australia. ·Palliat Support Care · Pubmed #28669376.

ABSTRACT: OBJECTIVE: People with pancreatic cancer have poor survival, and management is challenging. Pancreatic cancer patients' perceptions of their care coordination and its association with their outcomes have not been well-studied. Our objective was to determine if perception of care coordination is associated with patient-reported outcomes or survival. METHODS: People with pancreatic cancer who were 1-8 months postdiagnosis (52 with completed resection and 58 with no resection) completed a patient-reported questionnaire that assessed their perceptions of care coordination, quality of life, anxiety, and depression using validated instruments. Mean scores for 15 care-coordination items were calculated and then ranked from highest (best experience) to lowest (worst experience). Associations between care-coordination scores (including communication and navigation domains) and patient-reported outcomes and survival were investigated using general linear regression and Cox regression, respectively. All analyses were stratified by whether or not the tumor had been resected. RESULTS: In both groups, the highest-ranked care-coordination items were: knowing who was responsible for coordinating care, health professionals being informed about their history, and waiting times. The worst-ranked items related to: how often patients were asked about visits with other health professionals and how well they and their family were coping, knowing the symptoms they should monitor, having sufficient emotional help from staff, and access to additional specialist services. For people who had a resection, better communication and navigation scores were significantly associated with higher quality of life and less anxiety and depression. However, these associations were not statistically significant for those with no resection. Perception of cancer care coordination was not associated with survival in either group. SIGNIFICANCE OF RESULTS: Our results suggest that, while many core clinical aspects of care are perceived to be done well for pancreatic cancer patients, improvements in emotional support, referral to specialist services, and self-management education may improve patient-reported outcomes.

22 Article Anxiety, depression and quality of life in people with pancreatic cancer and their carers. 2017

Janda, Monika / Neale, Rachel E / Klein, Kerenaftali / O'Connell, Dianne L / Gooden, Helen / Goldstein, David / Merrett, Neil D / Wyld, David K / Rowlands, Ingrid J / Beesley, Vanessa L. ·Institute for Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia. · Population Health Department, QIMR Berghofer Medical Research Institute, Brisbane, Australia. · Cancer Research Division, Cancer Council NSW, Sydney, Australia. · Cancer Nursing Research Unit, University of Sydney, Sydney, Australia. · University of New South Wales, Sydney, Australia; Department of Medical Oncology, Prince of Wales Hospital, Sydney, Australia. · South Western Sydney Upper GI Surgical Unit, Bankstown Hospital, Sydney, Australia; Discipline of Surgery, University of Western Sydney, Sydney, Australia. · Department of Medical Oncology, Royal Brisbane and Women's Hospital, Brisbane, Australia; School of Medicine, University of Queensland, Brisbane, Australia. · School of Public Health, University of Queensland, Brisbane, Australia. · Population Health Department, QIMR Berghofer Medical Research Institute, Brisbane, Australia. Electronic address: Vanessa.Beesley@qimrberghofer.edu.au. ·Pancreatology · Pubmed #28153446.

ABSTRACT: BACKGROUND: People with pancreatic cancer have high levels of anxiety and depression and reduced quality of life (QoL), but few studies have assessed these outcomes for patient-carer dyads. We therefore investigated these issues in an Australian population-based study. METHODS: Patients with pancreatic cancer (n = 136) and many of their carers (n = 84) completed the Hospital Anxiety and Depression Scale (HADS) and Functional Assessment of Cancer Therapy QoL questionnaire at a median of three months after diagnosis. Overall QoL and well-being subscales (physical, social, emotional, functional) were compared with general population norms. Intraclass correlation coefficients were used to compare anxiety, depression and QoL scores of patients and their respective carers. RESULTS: Fifteen percent of patients and 39% of carers had HADS scores indicative of anxiety and 15% of patients and 14% of carers of depression, respectively. Overall, 70% of patients and 58% of carers had QoL scores below the Queensland population average. Patients' anxiety, depression, overall QoL, social, emotional and functional wellbeing scores were significantly related to those scores in their carers. Among patients and carers, accessing psychological help was associated with elevated anxiety. Not receiving chemotherapy was associated with elevated depression among patients and younger age was associated with poorer outcomes in carers. CONCLUSIONS: More carers had symptoms of anxiety than patients with pancreatic cancer, but symptoms of depression were similarly common in patients and carers. Further research is needed to assess whether interventions to reduce patients' distress could also improve QoL among carers, or whether carer-focussed interventions are required.

23 Article MutY-Homolog (MYH) inhibition reduces pancreatic cancer cell growth and increases chemosensitivity. 2017

Sharbeen, George / Youkhana, Janet / Mawson, Amanda / McCarroll, Joshua / Nunez, Andrea / Biankin, Andrew / Johns, Amber / Goldstein, David / Phillips, Phoebe. ·Pancreatic Cancer Translational Research Group, Lowy Cancer Research Centre, Prince of Wales Clinical School, University of New South Wales, Sydney, Australia. · Children's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales, Sydney, Australia. · Australian Centre for NanoMedicine, University of New South Wales, Sydney, Australia. · Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Bearsden, Glasgow, Scotland, United Kingdom. · The Kinghorn Cancer Centre, Cancer Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, Australia. ·Oncotarget · Pubmed #27999205.

ABSTRACT: Patients with pancreatic ductal adenocarcinoma (PC) have a poor prognosis due to metastases and chemoresistance. PC is characterized by extensive fibrosis, which creates a hypoxic microenvironment, and leads to increased chemoresistance and intracellular oxidative stress. Thus, proteins that protect against oxidative stress are potential therapeutic targets for PC. A key protein that maintains genomic integrity against oxidative damage is MutY-Homolog (MYH). No prior studies have investigated the function of MYH in PC cells. Using siRNA, we showed that knockdown of MYH in PC cells 1) reduced PC cell proliferation and increased apoptosis; 2) further decreased PC cell growth in the presence of oxidative stress and chemotherapy agents (gemcitabine, paclitaxel and vincristine); 3) reduced PC cell metastatic potential; and 4) decreased PC tumor growth in a subcutaneous mouse model in vivo. The results from this study suggest MYH may be a novel therapeutic target for PC that could potentially improve patient outcome by reducing PC cell survival, increasing the efficacy of existing drugs and reducing metastatic spread.

24 Article Factors associated with quality of care for patients with pancreatic cancer in Australia. 2016

Burmeister, Elizabeth A / O'Connell, Dianne L / Jordan, Susan J / Goldstein, David / Merrett, Neil / Wyld, David K / Beesley, Vanessa L / Gooden, Helen M / Janda, Monika / Neale, Rachel E. ·QIMR Berghofer Medical Research Institute, Brisbane, QLD elizabeth.burmeister@qimrberghofer.edu.au. · Cancer Council NSW, Sydney, NSW. · QIMR Berghofer Medical Research Institute, Brisbane, QLD. · Prince of Wales Hospital, Sydney, NSW. · University of Western Sydney, Penrith, NSW. · Royal Brisbane and Women's Hospital, Brisbane, QLD. · University of Sydney, Sydney, NSW. · Queensland University of Technology, Brisbane, QLD. ·Med J Aust · Pubmed #27852184.

ABSTRACT: OBJECTIVES: To develop a composite score for the quality of care for patients with pancreatic cancer in Australia; to determine whether it was affected by patient and health service-related factors; to assess whether the score and survival were correlated. DESIGN, PARTICIPANTS AND SETTING: We reviewed medical records of patients diagnosed with pancreatic cancer during July 2009 - June 2011 and notified to the Queensland and New South Wales cancer registries. DESIGN AND MAIN OUTCOME MEASURES: Participants were allocated proportional quality of care scores based on indicators derived from a Delphi process, ranging from 0 (lowest) to 1 (highest quality care). Associations between patient and health service-related factors and the score were tested by linear regression, and associations between the score and survival with Kaplan-Meier and Cox proportional hazards methods. RESULTS: Proportional quality of care scores were assigned to 1571 patients. Scores for patients living in rural areas were significantly lower than for those in major cities (adjusted difference, 11%; 95% CI, 8-13%); they were higher for patients in the least socio-economically disadvantaged areas (v most disadvantaged areas: 8% higher; 95% CI, 6-11%), who were younger, had better Eastern Cooperative Oncology Group performance status, or who first presented to a hospital with a high pancreatic case volume. Higher scores were associated with improved survival; after adjusting for patient-related factors, each 10 percentage point increase in the score reduced the risk of dying by 6% (hazard ratio, 0.94; 95% CI, 0.91-0.97). CONCLUSION: Geographic category of residence may influence the quality of care received by patients with pancreatic cancer, and survival could be improved if they received optimal care.

25 Article Refining the care of patients with pancreatic cancer: the AGITG Pancreatic Cancer Workshop consensus. 2016

Gandy, Robert C / Barbour, Andrew P / Samra, Jaswinder / Nikfarjam, Mehrdad / Haghighi, Koroush / Kench, James G / Saxena, Payal / Goldstein, David. ·Prince of Wales Hospital, Sydney, NSW d.goldstein@unsw.edu.au. · University of Queensland, Brisbane, QLD. · Royal North Shore Hospital, Sydney, NSW. · Austin Health, Melbourne, VIC. · Prince of Wales Hospital, Sydney, NSW. · Royal Prince Alfred Hospital, Sydney, NSW. ·Med J Aust · Pubmed #27318402.

ABSTRACT: A meeting of the Australasian Gastro-Intestinal Trials Group (AGITG) was held to develop a consensus statement defining when a patient with pancreatic cancer has disease that is clearly operable, is borderline, or is locally advanced/inoperable. Key issues included the need for multidisciplinary team consensus for all patients considered for surgical resection. Staging investigations, to be completed within 4 weeks of presentation, should include pancreatic protocol computed tomography, endoscopic ultrasound, and, when possible, biopsy. Given marked differences in outcomes, the operability of tumours should be clearly identified by categories: those clearly resectable by standard means (group 1a), those requiring vascular resection but which are clearly operable (group 1b), and those of borderline operability requiring vascular resection (groups 2a and 2b). Patients who may require vascular reconstruction should be referred, before exploration, to a specialist unit. All patients should have a structured pathology report with standardised reporting of all seven surgical margins, which identifies an R0 (no tumour cells within a defined distance of the margin) if all surgical margins are clear from 1 mm. Neo-adjuvant therapy is increasingly recommended for borderline operable disease, while chemotherapy is recommended as initial therapy for patients with unresectable loco-regional pancreatic cancer. The value of adding radiation after initial chemotherapy remains uncertain. A small number of patients may be downstaged by chemoradiation, and trimodality therapy should only be considered as part of a clinical trial. Instituting these recommendations nationally will be an integral part of the process of improving quality of care and reducing geographic variation between centres in outcomes for patients.

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