Denosumab in men receiving androgen-deprivation therapy for prostate cancer.
Denosumab in men receiving androgen-deprivation therapy for prostate cancer.
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DOI：
10.1056/nejmoa0809003
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发表时间：
2009-08-20
期刊：
影响因子：
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通讯作者：
Denosumab HALT Prostate Cancer Study Group
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文献类型：
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作者：
Smith MR;Egerdie B;Hernández Toriz N;Feldman R;Tammela TL;Saad F;Heracek J;Szwedowski M;Ke C;Kupic A;Leder BZ;Goessl C;Denosumab HALT Prostate Cancer Study Group
雄激素剥夺治疗是针对前列腺癌的良好的，但与骨质流失和骨折的风险增加有关。接受非转移性前列腺癌的雄激素剥夺疗法的男性的密度和断裂。
在这项双盲，多中心研究中，我们随机分配了每6个月或安慰剂皮下剂量的denosumab（每组734例）。 24个月的脊柱包括股骨颈部骨矿物质密度的百分比，在24个月和所有三个地点的总臀部变化，以及新的椎骨骨折事件。
在24个月中，腰椎的骨矿物质密度在Denosumab组中增加了5.6％，而安慰剂组的损失为1.0％（p <0.001）。 1个月并持续36个月。两组的骨折在36个月时（1.5％，安慰剂为3.9％）（相对风险，0.38； 95％的置信区间，0.19至0.78； p = 0.006）。
Denosumab与所有部位的骨矿物质密度增加有关，并且在接受雄激素剥夺治疗的男性中，新的椎骨骨折事件降低了非转移性前列腺癌（ClinicalTrials.gov数量，NCT00089674）。
Androgen-deprivation therapy is well-established for treating prostate cancer but is associated with bone loss and an increased risk of fracture. We investigated the effects of denosumab, a fully human monoclonal antibody against receptor activator of nuclear factor-κB ligand, on bone mineral density and fractures in men receiving androgen-deprivation therapy for nonmetastatic prostate cancer. In this double-blind, multicenter study, we randomly assigned patients to receive denosumab at a dose of 60 mg subcutaneously every 6 months or placebo (734 patients in each group). The primary end point was percent change in bone mineral density at the lumbar spine at 24 months. Key secondary end points included percent change in bone mineral densities at the femoral neck and total hip at 24 months and at all three sites at 36 months, as well as incidence of new vertebral fractures. At 24 months, bone mineral density of the lumbar spine had increased by 5.6% in the denosumab group as compared with a loss of 1.0% in the placebo group (P<0.001); significant differences between the two groups were seen at as early as 1 month and sustained through 36 months. Denosumab therapy was also associated with significant increases in bone mineral density at the total hip, femoral neck, and distal third of the radius at all time points. Patients who received denosumab had a decreased incidence of new vertebral fractures at 36 months (1.5%, vs. 3.9% with placebo) (relative risk, 0.38; 95% confidence interval, 0.19 to 0.78; P = 0.006). Rates of adverse events were similar between the two groups. Denosumab was associated with increased bone mineral density at all sites and a reduction in the incidence of new vertebral fractures among men receiving androgen-deprivation therapy for nonmetastatic prostate cancer. (ClinicalTrials.gov number, NCT00089674.)