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Toremifene to Reduce Fracture Risk in Men Receiving Androgen Deprivation Therapy for Prostate Cancer

2010; Lippincott Williams & Wilkins; Volume: 184; Issue: 4 Linguagem: Inglês

10.1016/j.juro.2010.06.022

1527-3792

Matthew Smith, Ronald A. Morton, K. Gary Barnette, Paul Sieber, S. Bruce Malkowicz, Domingo Rodriguez, Michael L. Hancock, Mitchell S. Steiner,

Bone health and osteoporosis research

No AccessJournal of UrologyAdult Urology1 Oct 2010Toremifene to Reduce Fracture Risk in Men Receiving Androgen Deprivation Therapy for Prostate Canceris corrected byErratumis companion ofToremifene to Reduce Fracture Risk in Men Receiving Androgen Deprivation Therapy for Prostate Cancer Matthew R. Smith, Ronald A. Morton, K. Gary Barnette, Paul R. Sieber, S. Bruce Malkowicz, Domingo Rodriguez, Michael L. Hancock, and Mitchell S. Steiner Matthew R. SmithMatthew R. Smith Massachusetts General Hospital Cancer Center, Boston, Massachusetts , Ronald A. MortonRonald A. Morton GTx Incorporated, Memphis, Tennessee , K. Gary BarnetteK. Gary Barnette GTx Incorporated, Memphis, Tennessee , Paul R. SieberPaul R. Sieber Urologic Associates of Lancaster, Lancaster, Pennsylvania , S. Bruce MalkowiczS. Bruce Malkowicz Division of Urology, Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania , Domingo RodriguezDomingo Rodriguez GTx Incorporated, Memphis, Tennessee , Michael L. HancockMichael L. Hancock GTx Incorporated, Memphis, Tennessee , and Mitchell S. SteinerMitchell S. Steiner GTx Incorporated, Memphis, Tennessee View All Author Informationhttps://doi.org/10.1016/j.juro.2010.06.022AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Androgen deprivation therapy is associated with fracture risk in men with prostate cancer. We assessed the effects of toremifene, a selective estrogen receptor modulator, on fracture incidence in men receiving androgen deprivation therapy during a 2-year period. Materials and Methods: In this double-blind, placebo controlled phase III study 646 men receiving androgen deprivation therapy for prostate cancer were assigned to toremifene (80 mg by mouth daily) and 638 were assigned to placebo. Subjects were followed for 2 years. The primary study end point was new vertebral fractures. Secondary end points included fragility fractures, bone mineral density and lipid changes. Results: The 2-year incidence of new vertebral fractures was 4.9% in the placebo group vs 2.5% in the toremifene group, a significant relative risk reduction of 50% (95% CI –1.5 to 75.0, p = 0.05). Toremifene significantly increased bone mineral density at the lumbar spine, hip and femoral neck vs placebo (p <0.0001 for all comparisons). There was a concomitant decrease in markers of bone turnover (p <0.05 for all comparisons). Toremifene also significantly improved lipid profiles. Venous thromboembolic events occurred more frequently with toremifene than placebo with 7 subjects (1.1%) in the placebo group experiencing a venous thromboembolic event vs 17 (2.6%) in the toremifene group. Other adverse events were similar between the groups. Conclusions: Toremifene significantly decreased the incidence of new vertebral fractures in men receiving androgen deprivation therapy for prostate cancer. It also significantly improved bone mineral density, bone turnover markers and serum lipid profiles. References 1 : Cancer statistics, 2008. CA Cancer J Clin2008; 58: 71. Google Scholar 2 : Androgen deprivation therapy for prostate cancer. JAMA2005; 294: 238. Google Scholar 3 : Increasing use of gonadotropin-releasing hormone agonists for the treatment of localized prostate carcinoma. Cancer2005; 103: 1615. Google Scholar 4 : Relative contributions of testosterone and estrogen in regulating bone resorption and formation in normal elderly men. J Clin Invest2000; 106: 1553. Crossref, Medline, Google Scholar 5 : Risk of fracture after androgen deprivation for prostate cancer. N Engl J Med2005; 352: 154. Google Scholar 6 : Gonadotropin-releasing hormone agonists and fracture risk: a claims-based cohort study of men with nonmetastatic prostate cancer. J Clin Oncol2005; 23: 7897. Google Scholar 7 : Men and osteoporosis. www.nof.org/men. Accessed July 14, 2010. Google Scholar 8 : The structural basis of bone fragility in men. Bone1999; 25: 143. Google Scholar 9 : Clinical practice: Osteoporosis in men. N Engl J Med2008; 358: 1474. Google Scholar 10 : Assessment of vertebral fractures in osteoporosis research. J Rheumatol1997; 24: 1212. Google Scholar 11 : Changes in body composition during androgen deprivation therapy for prostate cancer. J Clin Endocrinol Metab2002; 87: 599. Crossref, Medline, Google Scholar 12 : The protective effects of estrogen on the cardiovascular system. N Engl J Med1999; 340: 1801. Crossref, Medline, Google Scholar 13 : Complications of androgen deprivation therapy in prostate cancer. Curr Opin Urol2009; 19: 322. Google Scholar 14 : Toremifene: A review of its pharmacological properties and clinical efficacy in the management of advanced breast cancer. Drugs1997; 54: 141. Google Scholar 15 : Toremifene citrate versus placebo for treatment of bone loss and other complications of androgen deprivation therapy in patients with prostate cancer. abstract J Clin Oncol2004; 22. abstract 4597. Google Scholar 16 : SAS/STAT 9.1 User's Guide. Cary, North Carolina: SAS Institute, Inc2004. Google Scholar 17 : Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst1959; 22: 719. Medline, Google Scholar 18 : Statistical Methods in Cancer Research Volume 1- the Analysis of Case-Control Studies. IARC Scientific Publications No. 32 Lyon, France: International Agency for Research on Cancer1980. Google Scholar 19 : The analysis of several 2 x 2 contingency tables. Biometrika1971; 58: 129. Google Scholar 20 : Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial: Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators. JAMA1999; 282: 637. Google Scholar 21 : Raloxifene to prevent gonadotropin-releasing hormone agonist-induced bone loss in men with prostate cancer: a randomized controlled trial. J Clin Endocrinol Metab2004; 89: 3841. Google Scholar 22 : Randomized controlled trial of zoledronic acid to prevent bone loss in men undergoing androgen deprivation therapy for nonmetastatic prostate cancer. J Urol2003; 169: 2008. Link, Google Scholar 23 : Effect of once-weekly oral alendronate on bone loss in men receiving androgen deprivation therapy for prostate cancer: a randomized trial. Ann Intern Med2007; 146: 416. Google Scholar 24 : Denosumab in men receiving androgen-deprivation therapy for prostate cancer. N Engl J Med2009; 361: 745. Google Scholar 25 : Vertebral fractures predict subsequent fractures. Osteoporos Int1999; 10: 214. Google Scholar 26 : The effect of vertebral fracture as a risk factor for osteoporotic fracture and mortality in a Spanish population. Osteoporos Int2003; 14: 520. Google Scholar 27 : Diabetes and cardiovascular disease during androgen deprivation for prostate cancer. J Clin Oncol2006; 24: 4448. Google Scholar 28 : Metabolic complications of androgen deprivation therapy for prostate cancer. J Urol2009; 181: 1998. Link, Google Scholar © 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited byMorgans A, Hancock M, Barnette K, Steiner M, Morton R and Smith M (2012) Racial Differences in Bone Mineral Density and Fractures in Men Receiving Androgen Deprivation Therapy for Prostate CancerJournal of Urology, VOL. 187, NO. 3, (889-893), Online publication date: 1-Mar-2012.Smith M, Malkowicz S, Brawer M, Hancock M, Morton R and Steiner M (2011) Toremifene Decreases Vertebral Fractures in Men Younger Than 80 Years Receiving Androgen Deprivation Therapy for Prostate CancerJournal of Urology, VOL. 186, NO. 6, (2239-2244), Online publication date: 1-Dec-2011.Related articlesJournal of Urology18 Nov 2010ErratumJournal of Urology10 Nov 2018Toremifene to Reduce Fracture Risk in Men Receiving Androgen Deprivation Therapy for Prostate Cancer Volume 184Issue 4October 2010Page: 1316-1321 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.Keywordsprostatic neoplasmsosteoporosistoremifeneselective estrogen receptor modulatorsAcknowledgmentsDr. Michael Malia from Complete Publication Solutions provided editorial assistance supported by GTx, Inc.MetricsAuthor Information Matthew R. Smith Massachusetts General Hospital Cancer Center, Boston, Massachusetts Financial interest and/or other relationship with GTx, Inc. Recipient of a National Institutes of Health K24 Midcareer Investigator Award (5K24CA121990-02) and awards from the Prostate Cancer Foundation. More articles by this author Ronald A. Morton GTx Incorporated, Memphis, Tennessee Financial interest and/or other relationship with GTx, Inc. More articles by this author K. Gary Barnette GTx Incorporated, Memphis, Tennessee Financial interest and/or other relationship with GTx, Inc. More articles by this author Paul R. Sieber Urologic Associates of Lancaster, Lancaster, Pennsylvania Financial interest and/or other relationship with GTx and Amgen. More articles by this author S. Bruce Malkowicz Division of Urology, Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania Financial interest and/or other relationship with Astellas, Endo Pharma, Tengion and GTx. More articles by this author Domingo Rodriguez GTx Incorporated, Memphis, Tennessee Financial interest and/or other relationship with GTx, Inc. More articles by this author Michael L. Hancock GTx Incorporated, Memphis, Tennessee Financial interest and/or other relationship with GTx, Inc. More articles by this author Mitchell S. Steiner GTx Incorporated, Memphis, Tennessee Financial interest and/or other relationship with GTx, Inc. More articles by this author Expand All Advertisement PDF downloadLoading ...