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Pancreatic Neoplasms: HELP
Articles by John Bridgewater
Based on 6 articles published since 2009
(Why 6 articles?)
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Between 2009 and 2019, J. Bridgewater wrote the following 6 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Clinical Trial Study protocol: a multi-centre randomised study of induction chemotherapy followed by capecitabine ± nelfinavir with high- or standard-dose radiotherapy for locally advanced pancreatic cancer (SCALOP-2). 2019

Strauss, Victoria Y / Shaw, Rachel / Virdee, Pradeep S / Hurt, Christopher N / Ward, Elizabeth / Tranter, Bethan / Patel, Neel / Bridgewater, John / Parsons, Philip / Radhakrishna, Ganesh / O'Neill, Eric / Sebag-Montefiore, David / Hawkins, Maria / Corrie, Pippa G / Maughan, Timothy / Mukherjee, Somnath. ·Centre for Statistics in Medicine, University of Oxford, Oxford, UK. · Oncology Clinical Trials Office, University of Oxford, Oxford, UK. · Centre for Trials Research, Cardiff University, Cardiff, UK. · Clinical Trials and Evaluation Unit, Bristol Royal Infirmary, Bristol, UK. · Pharmacy Department, Velindre Cancer Centre, Velindre NHS University Trust, Cardiff, UK. · Department of Radiology, Oxford University Hospitals NHS Foundation Trust, Churchill Hospital, Oxford, UK. · Department of Oncology, University College London Hospitals, London, UK. · Cardiff NCRI RTTQA group, Department of Medical Physics, Velindre Cancer Centre, Cardiff, UK. · Oncology Department, The Christie NHS Foundation Trust, Wilmslow Road, Manchester, UK. · Department of Oncology, University of Oxford, CRUK MRC Oxford Institute for Radiation Oncology, Oxford, UK. · University of Leeds, Leeds Cancer Centre, St James's University Hospital, Leeds, UK. · Cambridge Cancer Centre, Addenbrooke's Hospital, Cambridge, UK. · Department of Oncology, University of Oxford, CRUK MRC Oxford Institute for Radiation Oncology, Oxford, UK. somnath.mukherjee@oncology.ox.ac.uk. ·BMC Cancer · Pubmed #30717707.

ABSTRACT: BACKGROUND: Induction chemotherapy followed by chemoradiation is a treatment option for patients with locally advanced pancreatic cancer (LAPC). However, overall survival is comparable to chemotherapy alone and local progression occurs in nearly half of all patients, suggesting chemoradiation strategies should be optimised. SCALOP-2 is a randomised phase II trial testing the role of radiotherapy dose escalation and/or the addition of the radiosensitiser nelfinavir, following induction chemotherapy of gemcitabine and nab-paclitaxel (GEMABX). A safety run-in phase (stage 1) established the nelfinavir dose to administer with chemoradiation in the randomised phase (stage 2). METHODS: Patients with locally advanced, inoperable, non-metastatic pancreatic adenocarcinoma receive three cycles of induction GEMABX chemotherapy prior to radiological assessment. Those with stable/responding disease are eligible for further trial treatment. In Stage 1, participants received one further cycle of GEMABX followed by capecitabine-chemoradiation with escalating doses of nelfinavir in a rolling-six design. Stage 2 aims to register 262 and randomise 170 patients with responding/stable disease to one of five arms: capecitabine with high- (arms C + D) or standard-dose (arms A + B) radiotherapy with (arms A + C) or without (arms B + D) nelfinavir, or three more cycles of GEMABX (arm E). Participants allocated to the chemoradiation arms receive another cycle of GEMABX before chemoradiation begins. Co-primary outcomes are 12-month overall survival (radiotherapy dose-escalation question) and progression-free survival (nelfinavir question). Secondary outcomes include toxicity, quality of life, disease response rate, resection rate, treatment compliance, and CA19-9 response. SCALOP-2 incorporates a detailed radiotherapy quality assurance programme. DISCUSSION: SCALOP-2 aims to optimise chemoradiation in LAPC and incorporates a modern induction regimen. TRIAL REGISTRATION: Eudract No: 2013-004968-56; ClinicalTrials.gov : NCT02024009.

2 Clinical Trial Phase I/II Study of Refametinib (BAY 86-9766) in Combination with Gemcitabine in Advanced Pancreatic cancer. 2017

Van Laethem, Jean-Luc / Riess, Hanno / Jassem, Jacek / Haas, Michael / Martens, Uwe M / Weekes, Colin / Peeters, Marc / Ross, Paul / Bridgewater, John / Melichar, Bohuslav / Cascinu, Stefano / Saramak, Piotr / Michl, Patrick / Van Brummelen, David / Zaniboni, Alberto / Schmiegel, Wollf / Dueland, Svein / Giurescu, Marius / Garosi, Vittorio L / Roth, Katrin / Schulz, Anke / Seidel, Henrik / Rajagopalan, Prabhu / Teufel, Michael / Childs, Barrett H. ·Department of Gastroenterology, Erasme University Hospital, CP 572/10, route de Lennik 808, 1070, Brussels, Belgium. JL.VanLaethem@erasme.ulb.ac.be. · Medical Department, Division of Hematology, Oncology and Tumor Immunology, Charity Hospital, Virchow-Klinikum Campus, Augustenburger Platz 1, 13353, Berlin, Germany. · Department of Oncology and Radiotherapy, Medical University of Gdansk, M. Skłodowskiej-Curie 3a Street, Gdansk, 80-210, Poland. · Department of Hematology and Oncology, University of Munich Medical Center, Marchioninistraße 15, 81366, Munich, Germany. · Department of Hematology and Oncology, Cancer Center Heilbronn-Franken, Am Gesundbrunnen 20-26, 74078, Heilbronn, Germany. · Division of Medical Oncology, University of Colorado Cancer Center, 1665 Aurora Ct, Aurora, CO, 80045, USA. · Department of Oncology, Antwerp University Hospital, Wilrijkstraat 10, 2650, Edegem, Belgium. · Department of Medical Oncology, Guy's & St Thomas' Hospital, Westminster Bridge Road, London, SE1 7EH, UK. · Department of Oncology, UCL Cancer Institute, 72 Huntley Street, London, WC1E 6DD, UK. · Department of Oncology, Palacky University Medical School and University Hospital Olomouc, Křížkovského 8, 771 47, Olomouc, Czech Republic. · Department of Medical Oncology, A.O.U. United Hospitals, Polytechnic University of Marche, Piazza Roma, 22, Ancona, Italy. · Department of Oncological Gastroenterology, Maria Skłodowska-Curie Memorial Cancer Center, ul. W.K. Roentgena 5, 02-781, Warsaw, Poland. · Department of Gastroenterology, Endocrinology, Metabolism and Infectiology, University Hospital of Giessen and Marburg, Baldingerstraße, 35043, Marburg, Germany. · Universitätsklinikum Halle - University Hospital Halle (Saale), Ernst-Grube-Straße 40, 06120, Halle (Saale), Germany. · Department of Radiotherapy, UZ Brussels, Avenue du Laerbeek 101, 1090, Brussels, Belgium. · Department of Medical Oncology, Poliambulanza Foundation Hospital Institute, Via Bissolati, 57, Brescia, Italy. · Department of Gastroenterology and Hepatology, Medical University Hospital Bochum, Alexandrinenstraße 1, Bochum, 44791, Germany. · Department of Oncology, Oslo University Radium Hospital, Trondheimsveien 235, Bjerke, 0514, Oslo, Norway. · Bayer Pharma AG, Müllerstraße 178, 13353, Berlin, Germany. · Bayer S.p.A., Viale Certosa 126-130, 20156, Milan, Italy. · Bayer HealthCare Pharmaceuticals, Inc., 100 Bayer Blvd, Whippany, NJ, 07981, USA. ·Target Oncol · Pubmed #27975152.

ABSTRACT: BACKGROUND: Activating KRAS mutations are reported in up to 90% of pancreatic cancers. Refametinib potently inhibits MEK1/2, part of the MAPK signaling pathway. This phase I/II study evaluated the safety and efficacy of refametinib plus gemcitabine in patients with advanced pancreatic cancer. METHODS: Phase I comprised dose escalation, followed by phase II expansion. Refametinib and gemcitabine plasma levels were analyzed for pharmacokinetics. KRAS mutational status was determined from circulating tumor DNA. RESULTS: Ninety patients overall received treatment. The maximum tolerated dose was refametinib 50 mg twice daily plus standard gemcitabine (1000 mg/m CONCLUSION: Refametinib plus gemcitabine was well tolerated, with a promising objective response rate, and had an acceptable safety profile and no pharmacokinetic interaction. There was a trend towards improved outcomes in patients without detectable KRAS mutations that deserves future investigation.

3 Clinical Trial Health-Related Quality of Life in SCALOP, a Randomized Phase 2 Trial Comparing Chemoradiation Therapy Regimens in Locally Advanced Pancreatic Cancer. 2015

Hurt, Christopher N / Mukherjee, Somnath / Bridgewater, John / Falk, Stephen / Crosby, Tom / McDonald, Alec / Joseph, George / Staffurth, John / Abrams, Ross A / Blazeby, Jane M / Bridges, Sarah / Dutton, Peter / Griffiths, Gareth / Maughan, Tim / Johnson, Colin. ·Wales Cancer Trials Unit, College of Biomedical and Life Sciences, Cardiff University, Cardiff, Wales, United Kingdom. Electronic address: hurtcn@cardiff.ac.uk. · Cancer Research UK/MRC Oxford Institute for Radiation Oncology, Oxford University, NIHR Biomedical Research, Oxford, United Kingdom. · UCL Cancer Institute, London, United Kingdom. · Bristol Haematology and Oncology Centre, Bristol, United Kingdom. · Velindre Cancer Centre, Velindre Hospital, Cardiff, Wales, United Kingdom. · Beatson West of Scotland Cancer Centre, Glasgow, Scotland, United Kingdom. · Institute of Cancer and Genetics, Cardiff University, Cardiff, Wales, United Kingdom. · Department of Radiation Oncology, Rush University Medical Center, Chicago, Illinois. · Division of Surgery, Head and Neck, University Hospitals Bristol National Health Service Foundation Trust, Bristol and School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom. · Wales Cancer Trials Unit, College of Biomedical and Life Sciences, Cardiff University, Cardiff, Wales, United Kingdom. · Centre for Statistics in Medicine, University of Oxford, Oxford, United Kingdom. · Southampton Clinical Trials Unit, Faculty of Medicine, Southampton University, Southampton General Hospital, Southampton, United Kingdom. · University Surgical Unit, Faculty of Medicine, University Hospital Southampton, Southampton, United Kingdom. ·Int J Radiat Oncol Biol Phys · Pubmed #26530749.

ABSTRACT: PURPOSE: Chemoradiation therapy (CRT) for patients with locally advanced pancreatic cancer (LAPC) provides survival benefits but may result in considerable toxicity. Health-related quality of life (HRQL) measurements during CRT have not been widely reported. This paper reports HRQL data from the Selective Chemoradiation in Advanced Localised Pancreatic Cancer (SCALOP) trial, including validation of the QLQ-PAN26 tool in CRT. METHODS AND MATERIALS: Patients with locally advanced, inoperable, nonmetastatic carcinoma of the pancreas were eligible. Following 12 weeks of induction gemcitabine plus capecitabine (GEMCAP) chemotherapy, patients with stable and responding disease were randomized to a further cycle of GEMCAP followed by capecitabine- or gemcitabine-based CRT. HRQL was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the EORTC Pancreatic Cancer module (PAN26). RESULTS: A total of 114 patients from 28 UK centers were registered and 74 patients randomized. There was improvement in the majority of HRQL scales during induction chemotherapy. Patients with significant deterioration in fatigue, appetite loss, and gastrointestinal symptoms during CRT recovered within 3 weeks following CRT. Differences in changes in HRQL scores between trial arms rarely reached statistical significance; however, where they did, they favored capecitabine therapy. PAN26 scales had good internal consistency and were able to distinguish between subgroups of patients experiencing toxicity. CONCLUSIONS: Although there is deterioration in HRQL following CRT, this resolves within 3 weeks. HRQL data support the use of capecitabine- over gemcitabine-based chemoradiation. The QLQ-PAN26 is a reliable and valid tool for use in patients receiving CRT.

4 Clinical Trial Phase II, randomized, biomarker identification trial (MARK) for erlotinib in patients with advanced pancreatic carcinoma. 2014

Propper, D / Davidenko, I / Bridgewater, J / Kupcinskas, L / Fittipaldo, A / Hillenbach, C / Klughammer, B / Ducreux, M. ·Barts Cancer Institute, Queen Mary University of London, London, UK d.j.propper@qmul.ac.uk. · State Medical Institution Clinical Oncology Dispensary, Krasnodar, Russia. · University College London Cancer Institute, London, UK. · Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania. · Roche Products Ltd, Welwyn Garden City, UK. · F. Hoffmann-La Roche Ltd, Basel, Switzerland. · Institut Gustave Roussy, Villejuif, France. ·Ann Oncol · Pubmed #24827134.

ABSTRACT: BACKGROUND: A prospective, randomized phase II study, with mandatory tumor sampling at current disease stage, aimed to identify biomarkers predictive of improved progression-free survival (PFS) in patients with pancreatic cancer treated with erlotinib. PATIENTS AND METHODS: Patients with histologically/cytologically confirmed, unresectable, locally advanced/metastatic pancreatic cancer, who had failed on or were unsuitable for first-line chemotherapy, underwent a tumor biopsy and were then randomized to receive once-daily erlotinib 150 mg or placebo. The primary end point was identification of biomarkers predicting improved PFS with erlotinib. Secondary end points included PFS, overall survival, response and toxicity. RESULTS: At data cut-off, 207 patients were enrolled and analyzed. Prespecified biomarker analyses of EGFR protein expression, EGFR gene copy number/mutations/polymorphisms and KRAS mutations did not identify any subgroups with a detrimental effect or a strong benefit for PFS with erlotinib. In the primary analysis, the median PFS was 6.1 versus 5.9 weeks in the erlotinib and placebo arms, respectively [hazard ratio (HR) 0.83; 95% confidence interval (CI) 0.63-1.10; P = 0.1909]. However, observed baseline imbalances indicated worse prognosis in the erlotinib arm. After adjustment for baseline characteristics, a significant PFS benefit for erlotinib was observed (HR 0.68; 95% CI 0.50-0.91; P = 0.0102). Exploratory biomarker analyses showed patients with high baseline serum amphiregulin levels might benefit from erlotinib. CONCLUSION: This study in patients with inoperable pancreatic cancer did not identify any prespecified biomarkers predictive of PFS benefit with erlotinib. Exploratory analyses suggested high amphiregulin might predict PFS benefit from erlotinib. CLINICALTRIALSGOV NUMBER: NCT00674973.

5 Clinical Trial Gemcitabine-based or capecitabine-based chemoradiotherapy for locally advanced pancreatic cancer (SCALOP): a multicentre, randomised, phase 2 trial. 2013

Mukherjee, Somnath / Hurt, Christopher N / Bridgewater, John / Falk, Stephen / Cummins, Sebastian / Wasan, Harpreet / Crosby, Tom / Jephcott, Catherine / Roy, Rajarshi / Radhakrishna, Ganesh / McDonald, Alec / Ray, Ruby / Joseph, George / Staffurth, John / Abrams, Ross A / Griffiths, Gareth / Maughan, Tim. ·Gray Institute for Radiation Oncology and Biology, University of Oxford, NIHR Oxford Biomedical Research Centre, Oxford, UK. somnath.mukherjee@oncology.ox.ac.uk ·Lancet Oncol · Pubmed #23474363.

ABSTRACT: BACKGROUND: In the UK, chemotherapy is the standard treatment for inoperable, locally advanced, non-metastatic pancreatic cancer. Chemoradiotherapy is also an acceptable treatment option, for which gemcitabine, fluorouracil, or capecitabine can be used as concurrent chemotherapy agents. We aimed to assess the activity, safety, and feasibility of both gemcitabine-based and capecitabine-based chemoradiotherapy after induction chemotherapy for patients with locally advanced pancreatic cancer. METHODS: In this open-label, randomised, two-arm, phase 2 trial, patients aged 18 years or older with histologically proven, locally advanced pancreatic cancer (with a tumour diameter of 7 cm or less) were recruited from 28 UK centres between Dec 24, 2009 and Oct 25, 2011. After 12 weeks of induction gemcitabine and capecitabine chemotherapy (three cycles of gemcitabine [1000 mg/m(2) on days 1, 8, 15 of a 28-day cycle] and capecitabine [830 mg/m(2) twice daily on days 1-21 of a 28-day cycle]), patients with stable or responding disease, tumour diameter of 6 cm or less, and WHO performance status 0-1 were randomly assigned to receive a further cycle of gemcitabine and capecitabine chemotherapy followed by either gemcitabine (300 mg/m(2) once per week) or capecitabine (830 mg/m(2) twice daily, Monday to Friday only), both in combination with radiation (50·4 Gy in 28 fractions). Randomisation (1:1) was done via a central computerised system and used stratified minimisation. The primary endpoint was 9-month progression-free survival, analysed by intention to treat including only those patients with valid CT assessments. This trial is registered with ISRCTN, number 96169987. FINDINGS: 114 patients were registered and 74 were randomly allocated (38 to the gemcitabine group and 36 to the capecitabine group). After 9 months, 22 of 35 assessable patients (62·9%, 80% CI 50·6-73·9) in the capecitabine group and 18 of 35 assessable patients (51·4%, 39·4-63·4) in the gemcitabine group had not progressed. Median overall survival was 15·2 months (95% CI 13·9-19·2) in the capecitabine group and 13·4 months (95% CI 11·0-15·7) in the gemcitabine group (adjusted hazard ratio [HR] 0·39, 95% CI 0·18-0·81; p=0·012). 12-month overall survival was 79·2% (95% CI 61·1-89·5) in the capecitabine group and 64·2 (95% CI 46·4-77·5) in the gemcitabine group. Median progression-free survival was 12·0 months (95% CI 10·2-14·6) in the capecitabine group and 10·4 months (95% CI 8·9-12·5) in the gemcitabine group (adjusted HR 0·60, 95% CI 0·32-1·12; p=0·11). Eight patients in the capecitabine group had an objective response at 26 weeks, as did seven in the gemcitabine group. More patients in the gemcitabine group than in the capecitabine group had grade 3-4 haematological toxic effects (seven [18%] vs none, p=0·008) and non-haematological toxic effects (ten [26%] vs four [12%], p=0·12) during chemoradiation treatment; the most frequent events were leucopenia, neutropenia, and fatigue. Two patients in the capecitabine group progressed during the fourth cycle of induction chemotherapy. Of the 34 patients in the capecitabine group who received chemoradiotherapy, 25 (74%) received the full protocol dose of radiotherapy, compared with 26 (68%) of 38 patients in the gemcitabine group. Quality-of-life scores were not significantly different between the treatment groups. INTERPRETATION: Our results suggest that a capecitabine-based regimen might be preferable to a gemcitabine-based regimen in the context of consolidation chemoradiotherapy after a course of induction chemotherapy for locally advanced pancreatic cancer. However, these findings should be interpreted with caution because the difference in the primary endpoint was non-significant and the number of patients in the trial was small. FUNDING: Cancer Research UK.

6 Article Chemoradiotherapy with or without induction chemotherapy for locally advanced pancreatic cancer: a UK multi-institutional experience. 2010

Gillmore, R / Laurence, V / Raouf, S / Tobias, J / Blackman, G / Meyer, T / Goodchild, K / Collis, C / Bridgewater, J. ·University College Hospital, University College London Cancer Institute, London, UK. ·Clin Oncol (R Coll Radiol) · Pubmed #20605709.

ABSTRACT: AIMS: The optimal management for patients with unresectable locally advanced adenocarcinoma of the pancreas (LAPC) is unclear. The aim of this study was to determine the outcome of patients treated with chemoradiotherapy (CRT) with or without induction chemotherapy. MATERIALS AND METHODS: We conducted a multi-centre retrospective analysis of 48 patients with biopsy-proven LAPC treated with CRT in four regional oncology centres in the UK between March 2000 and October 2007. The prescribed radiotherapy dose was 4500-5040 cGy in 25-28 fractions and was given concurrent with gemcitabine (n=37), gemcitabine/cisplatin (n=9), 5-fluorouracil (n=1) or capecitabine (n=1). RESULTS: Four patients (8.3%) did not complete the intended treatment due to CRT-related toxicities. The disease control rate (Objective response rate (ORR) and stable disease (SD)) was 81.3%. The median overall survival was 17 months (range 5-66 months). In subgroup analysis, a trend towards improved survival was seen in patients who completed the intended treatment (17.1 months vs 11.0 months, P=0.06) and in patients undergoing surgery (27 months vs 16 months, P=0.023). CONCLUSIONS: This is the largest reported series from the UK focussing on patients who received CRT for pancreas cancer. It shows that it is possible to deliver pancreatic CRT with acceptable toxicity. Induction chemotherapy followed by gemcitabine-based CRT shows promising activity and should be evaluated in phase III studies.