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.
RCT Entities:
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.
Authors: Matthew R Smith; Won Chan Lee; Jane Brandman; Qin Wang; Marc Botteman; Chris L Pashos Journal: J Clin Oncol Date: 2005-11-01 Impact factor: 44.544
Authors: B Ettinger; D M Black; B H Mitlak; R K Knickerbocker; T Nickelsen; H K Genant; C Christiansen; P D Delmas; J R Zanchetta; J Stakkestad; C C Glüer; K Krueger; F J Cohen; S Eckert; K E Ensrud; L V Avioli; P Lips; S R Cummings Journal: JAMA Date: 1999-08-18 Impact factor: 56.272
Authors: M Naves; J B Díaz-López; C Gómez; A Rodríguez-Rebollar; M Rodríguez-García; J B Cannata-Andía Journal: Osteoporos Int Date: 2003-04-25 Impact factor: 4.507
Authors: Matthew R Smith; James Eastham; Donald M Gleason; Daniel Shasha; Simon Tchekmedyian; Norman Zinner Journal: J Urol Date: 2003-06 Impact factor: 7.450
Authors: Matthew R Smith; S Bruce Malkowicz; Michael K Brawer; Michael L Hancock; Ronald A Morton; Mitchell S Steiner Journal: J Urol Date: 2011-10-19 Impact factor: 7.450