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Chemotherapy and Radiotherapy for Advanced Pancreatic Cancer (Review)

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Chemotherapy and Radiotherapy for Advanced Pancreatic Cancer (Review) View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Enlighten Cochrane Database of Systematic Reviews Chemotherapy and radiotherapy for advanced pancreatic cancer (Review) Chin V, Nagrial A, Sjoquist K, O’Connor CA, Chantrill L, Biankin AV, Scholten RJPM, Yip D Chin V, Nagrial A, Sjoquist K, O’Connor CA, Chantrill L, Biankin AV, Scholten RJPM, Yip D. Chemotherapy and radiotherapy for advanced pancreatic cancer. Cochrane Database of Systematic Reviews 2018, Issue 3. Art. No.: CD011044. DOI: 10.1002/14651858.CD011044.pub2. www.cochranelibrary.com Chemotherapy and radiotherapy for advanced pancreatic cancer (Review) Copyright © 2018 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. TABLE OF CONTENTS HEADER....................................... 1 ABSTRACT ...................................... 1 PLAINLANGUAGESUMMARY . 2 SUMMARY OF FINDINGS FOR THE MAIN COMPARISON . ..... 4 BACKGROUND .................................... 6 OBJECTIVES ..................................... 7 METHODS ...................................... 7 RESULTS....................................... 10 Figure1. ..................................... 11 Figure2. ..................................... 15 Figure3. ..................................... 16 ADDITIONALSUMMARYOFFINDINGS . 22 DISCUSSION ..................................... 28 AUTHORS’CONCLUSIONS . 30 ACKNOWLEDGEMENTS . 31 REFERENCES ..................................... 31 CHARACTERISTICSOFSTUDIES . 45 DATAANDANALYSES. 112 Analysis 1.1. Comparison 1 Anti-cancer therapy versus best supportive care, Outcome 1 Overall survival. 116 Analysis 2.1. Comparison 2 Various types of chemotherapy versus gemcitabine, Outcome 1 Overall survival. 117 Analysis 2.2. Comparison 2 Various types of chemotherapy versus gemcitabine, Outcome 2 Progression-free survival. 118 Analysis 2.3. Comparison 2 Various types of chemotherapy versus gemcitabine, Outcome 3 Degradation of QoL at 6 months..................................... 119 Analysis 2.4. Comparison 2 Various types of chemotherapy versus gemcitabine, Outcome 4 Response rates. 120 Analysis 2.5. Comparison 2 Various types of chemotherapy versus gemcitabine, Outcome 5 Grade 3/4 anaemia. 121 Analysis 2.6. Comparison 2 Various types of chemotherapy versus gemcitabine, Outcome 6 Grade 3/4 neutropenia. 123 Analysis 2.7. Comparison 2 Various types of chemotherapy versus gemcitabine, Outcome 7 Grade 3/4 thrombocytopenia. 124 Analysis 2.8. Comparison 2 Various types of chemotherapy versus gemcitabine, Outcome 8 Grade 3/4 nausea. 126 Analysis 2.9. Comparison 2 Various types of chemotherapy versus gemcitabine, Outcome 9 Grade 3/4 diarrhoea. 127 Analysis 3.1. Comparison 3 Gemcitabine combinations versus gemcitabine alone, Outcome 1 Overall survival. 128 Analysis 3.2. Comparison 3 Gemcitabine combinations versus gemcitabine alone, Outcome 2 Progression-free survival. 130 Analysis 3.3. Comparison 3 Gemcitabine combinations versus gemcitabine alone, Outcome 3 Response rates. 132 Analysis 3.4. Comparison 3 Gemcitabine combinations versus gemcitabine alone, Outcome 4 Grade 3/4 anaemia. 134 Analysis 3.5. Comparison 3 Gemcitabine combinations versus gemcitabine alone, Outcome 5 Grade 3/4 neutropenia. 136 Analysis 3.6. Comparison 3 Gemcitabine combinations versus gemcitabine alone, Outcome 6 Grade 3/4 thrombocytopenia. 138 Analysis 3.7. Comparison 3 Gemcitabine combinations versus gemcitabine alone, Outcome 7 Grade 3/4 nausea. 140 Analysis 3.8. Comparison 3 Gemcitabine combinations versus gemcitabine alone, Outcome 8 Grade 3/4 diarrhoea. 142 Analysis 3.9. Comparison 3 Gemcitabine combinations versus gemcitabine alone, Outcome 9 Grade 3/4 neuropathy. 143 Analysis 3.10. Comparison 3 Gemcitabine combinations versus gemcitabine alone, Outcome 10 Grade 3/4 fatigue. 144 Analysis 4.1. Comparison 4 Fluoropyrimidine combinations versus fluoropyrimidine alone, Outcome 1 Overall survival. 145 Analysis 4.2. Comparison 4 Fluoropyrimidine combinations versus fluoropyrimidine alone, Outcome 2 Progression-free survival..................................... 146 Analysis 4.3. Comparison 4 Fluoropyrimidine combinations versus fluoropyrimidine alone, Outcome 3 Response rates. 146 Analysis 4.4. Comparison 4 Fluoropyrimidine combinations versus fluoropyrimidine alone, Outcome 4 Grade 3/4 anaemia. ................................... 147 Analysis 4.5. Comparison 4 Fluoropyrimidine combinations versus fluoropyrimidine alone, Outcome 5 Grade 3/4 neutropenia. .................................. 148 Analysis 4.6. Comparison 4 Fluoropyrimidine combinations versus fluoropyrimidine alone, Outcome 6 Grade 3/4 thrombocytopenia. 149 Chemotherapy and radiotherapy for advanced pancreatic cancer (Review) i Copyright © 2018 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. Analysis 4.7. Comparison 4 Fluoropyrimidine combinations versus fluoropyrimidine alone, Outcome 7 Grade 3/4 fatigue..................................... 149 Analysis 4.8. Comparison 4 Fluoropyrimidine combinations versus fluoropyrimidine alone, Outcome 8 Grade 3/4 nausea..................................... 150 Analysis 4.9. Comparison 4 Fluoropyrimidine combinations versus fluoropyrimidine alone, Outcome 9 Grade 3/4 diarrhoea. ................................... 151 ADDITIONALTABLES. 151 APPENDICES ..................................... 159 HISTORY....................................... 162 CONTRIBUTIONSOFAUTHORS . 162 DECLARATIONSOFINTEREST . 163 SOURCESOFSUPPORT . 163 DIFFERENCES BETWEEN PROTOCOL AND REVIEW . .... 164 Chemotherapy and radiotherapy for advanced pancreatic cancer (Review) ii Copyright © 2018 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. [Intervention Review] Chemotherapy and radiotherapy for advanced pancreatic cancer Venessa Chin1,2, Adnan Nagrial1,3, Katrin Sjoquist4,5, Chelsie A O’Connor2,6,7, Lorraine Chantrill8, Andrew V Biankin9,10,11, Rob JPM Scholten12, Desmond Yip13,14 1The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, Australia. 2St Vincent’s Hospital, Sydney, Australia. 3The Crown Princess Mary Cancer Centre, Westmead, Australia. 4NHMRC Clinical Trials Centre, University of Sydney, Sydney, Australia. 5Medical Oncology, Cancer Care Centre, St George Hospital, Kogarah, Australia. 6Genesis Cancer Care, Sydney, Australia. 7Macquarie University Hospital, Sydney, Australia. 8Department of Pancreatic Cancer, The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, Australia. 9Institute of Cancer Sciences, University of Glasgow, Glasgow, UK. 10South Western Sydney Clinical School, Faculty of Medicine, University of New South Wales, Liverpool, Australia. 11West of Scotland Pancreatic Unit and Glasgow Royal Infirmary, Glasgow, UK. 12Cochrane Netherlands, Julius Center for Health Sciences and Primary Care / University Medical Center Utrecht, Utrecht, Netherlands. 13Department of Medical Oncology, The Canberra Hospital, Garran, Australia. 14ANU Medical School, Australian National University, Acton, Australia Contact address: Venessa Chin, The Kinghorn Cancer Centre, Garvan Institute of Medical Research, 384 Victoria Street Darlinghurst, Sydney, NSW, 2010, Australia. [email protected], [email protected]. Editorial group: Cochrane Upper GI and Pancreatic Diseases Group. Publication status and date: New, published in Issue 3, 2018. Citation: Chin V, Nagrial A, Sjoquist K, O’Connor CA, Chantrill L, Biankin AV, Scholten RJPM, Yip D. Chemotherapy and radiotherapy for advanced pancreatic cancer. Cochrane Database of Systematic Reviews 2018, Issue 3. Art. No.: CD011044. DOI: 10.1002/14651858.CD011044.pub2. Copyright © 2018 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. ABSTRACT Background Pancreatic cancer (PC) is a highly lethal disease with few effective treatment options. Over the past few decades, many anti-cancer therapies have been tested in the locally advanced and metastatic setting, with mixed results. This review attempts to synthesise all the randomised data available to help better inform patient and clinician decision-making when dealing with this difficult disease. Objectives To assess the effect of chemotherapy, radiotherapy or both for first-line treatment of advanced pancreatic cancer. Our primary outcome was overall survival, while secondary outcomes include progression-free survival, grade 3/4 adverse events, therapy response and quality of life. Search methods We searched for published and unpublished studies in CENTRAL (searched 14 June 2017), Embase (1980 to 14 June 2017), MEDLINE (1946 to 14 June 2017) and CANCERLIT (1999 to 2002) databases. We also handsearched all relevant conference abstracts published up until 14 June 2017. Selection criteria All randomised studies assessing overall survival outcomes in patients with advanced pancreatic ductal adenocarcinoma. Chemotherapy and radiotherapy, alone or in combination, were the eligible treatments. Chemotherapy and radiotherapy for advanced pancreatic cancer (Review) 1 Copyright © 2018 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. Data collection and analysis Two review authors independently analysed studies, and a third settled any disputes. We extracted data on overall survival (OS), progression-free survival (PFS), response rates, adverse events (AEs) and quality of life (QoL), and we assessed risk of bias for each study. Main results We included 42 studies addressing chemotherapy in 9463 patients with advanced pancreatic cancer. We did not identify any eligible studies on radiotherapy. We did not find any benefit
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