Centre for Reviews and Dissemination A Systematic Review of Parenteral Oestrogens for Prostate Cancer Parenteral Oestrogens for Prostate Cancer: A Systematic Review of Clinical Effectiveness and Dose Response 33 Promoting the use of research based knowledge REPORT 33 CRD Parenteral oestrogens for prostate cancer: A systematic review of clinical effectiveness and dose response Michael Emmans Dean2 Gill Norman1 Zoé Hodges6 Gill Ritchie3 Kate Light1 Alison Eastwood1 Ruth Langley4 Matthew Sydes4 Mahesh Parmar4 Paul Abel5 1 Centre for Reviews and Dissemination, University of York, York YO10 5DD 2 Department of Health Sciences, University of York, York YO10 5DD 3National Collaborating Centre for Primary Care, Frazer House, 32-38 Leman Street, London, E1 8EW 4MRC Clinical Trials Unit, 222 Euston Road, London 5Imperial College, London, W12 0NN 6 Department of Public Health and Policy, London School of Hygiene and Tropical Medicine, London, WC1B 3RE September 2006 © 2006 Centre for Reviews and Dissemination, University of York ISBN 1 900640 37 6 This report can be ordered from: Publications Office, Centre for Reviews and Dissemination, University of York, York YO10 5DD. 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Introduction…………………………………………………………………………………………. 1 2. Review Questions…………………………………………………………………………………... 3 3. Methods……………………………………………………………………………………………... 4 4. Results………………………………………………………………………………………………. 8 5. Discussion…………………………………………………………………………………………... 31 6. Conclusions…………………………………………………………………………………………. 34 References……………………………………………………………………………………………… 35 Appendix 1: Search Strategies……………………………………………………………………….. 38 Appendix 2: Data Extraction Form…………………………………………………………………… 58 Appendix 3: Quality Assessment Proforma…………………………………………………………. 59 Appendix 4: List of Abbreviations……………………………………………………………………. 60 Appendix 5: Stages and Grades……………………………………………………………………... 61 Appendix 6: List of Excluded Studies… …………………………………………………………… 63 Appendix 7: Data Extraction Tables……………… ……………………………………………… 66 List of Tables Table 1: Interventions and comparators……………………………………………………………. 9 Table 2: Summary of studies using parenteral oestrogen and reporting survival data………... 17 Table 3: Summary of studies using parenteral oestrogen in combination and reporting survival data………………………………………………………………………………… 20 Table 4: Cardiovascular events and deaths reported in studies employing parenteral oestrogen……………………………………………………………………………………. 23 Table 5: Cardiovascular events and deaths reported in studies employing parenteral oestrogen in combination………………………………………………………………….. 26 Table 6: Summary of studies using parenteral oestrogen and reporting testosterone data….. 28 Table 7: Summary of study using parenteral oestrogen in combination and reporting testosterone data…………………………………………………………………………… 30 List of Figures Figure 1: Summary of study identification, retrieval and inclusion/exclusion…………………… 8/9 Figure 2: Overall mortality in trials employing parenteral oestrogen alone in which data 18 were fully reported………………………………………………………………………… Figure 3: Prostate cancer mortality in trials employing parenteral oestrogen alone in which 18 data were fully reported…………………………………………………………………… Figure 4: Overall survival in trials using parenteral oestrogens in combination with oral 21 oestrogens in which data were fully reported…………………………………………… Figure 5: Cancer mortality in trials using parenteral oestrogens in combination with oral 21 oestrogens for which data could reliably be extracted…………………………………. Figure 6: Cardiovascular mortality in trials involving parenteral oestrogen alone 24 for which data were fully reported………………………………………………………... Figure 7: Cardiovascular morbidity in trials involving parenteral oestrogen alone 24 for which data were fully reported ………………………………………………………. Figure 8: Cardiovascular mortality in trials using parenteral oestrogens in combination with 27 oral oestrogens in which data were fully reported……………………………………... Figure 9: Cardiovascular morbidity in trials using parenteral oestrogens in combination with 27 oral oestrogens in which data were fully reported……………………………………... iv Executive Summary Objectives This review was undertaken to inform the design of a clinical trial using transdermal oestrogen patches in prostate cancer. The main objectives were: 1. To examine the clinical effectiveness and safety of parenteral oestrogen therapy in prostate cancer. 2. To examine the relationship between dose and efficacy and safety of parenteral oestrogen in prostate cancer. 3. To compare the safety profile of oestrogen given transdermally with other routes of administration, in males or male-to-female transsexuals with any condition. Methods Search strategy Eighteen electronic databases including EMBASE and MEDLINE were searched from inception to March 2004. Appropriate paper and internet resources were also searched. Inclusion/exclusion criteria Objective 1: Randomised controlled trials of parenteral oestrogen compared with any treatment in patients diagnosed