一年两次的denosumab治疗，阻止骨质丢失，增加骨密度，可防止接受激素抑制疗法的前列腺癌患者发生骨折。

Twice-yearly treatment with denosumab, a new targeted therapy to stop bone loss, increased bone density and prevented spinal fractures in men receiving androgen-deprivation therapy for prostate cancer. The report from an international research study, the first to document reduced fracture risk in men receiving the hormone-blocking treatment, will appear in the August 20 New England Journal of Medicine and is receiving early online release.

"Androgen-deprivation therapy is the standard treatment for men with locally advanced, recurrent and metastatic prostate cancer; but many active men who have been successfully treated for their cancer develop debilitating bone fractures as a result," says Matthew Smith, MD, PhD, of the Massachusetts General Hospital (MGH) Cancer Center, who led the study as part of the Denosumab HALT Prostate Cancer Study Group. "The results of this study should be critically important in improving the quality of life of thousands of prostate cancer survivors."

About one third of the two million prostate cancer survivors in the U.S. currently receive androgen-deprivation therapy, which blocks the release of testosterone. Several medications used to treat osteoporosis, including the drugs called bisphosphonates, have been shown to reduce androgen-deprivation-related bone loss in men in earlier small clinical studies, but none of those trials were adequate to demonstrate reduced fracture risk. Denosumab – a fully human monoclonal antibody that blocks the action of osteoclasts, the cells that break down bone in the normal process of bone remodeling – is also being investigated to prevent fractures in women with osteoporosis. The current study was a Phase 3 trial supporting the application for FDA approval filed by Amgen Inc., the primary sponsor of the NEJM report.

Men undergoing androgen-deprivation therapy for nonmetastatic prostate cancer were enrolled at 156 centers in North America and Europe and randomly assigned to receive injections of either denosumab or a placebo every six months for three years. Participants were also instructed to take daily calcium and vitamin D supplements during the study period.

Among the more than 900 participants who completed the study, denosumab significantly increased bone density at all the monitored sites – including the lumbar spine, total hip and femoral neck – and reduced new vertebral fractures by 62 percent. Bone density at the radius, one of the bones in the forearm, also increased in the treatment group, an improvement not seen with other osteoporosis drugs. Few adverse events were associated with treatment, and there were no reports of osteonecrosis of the jaw, a problem reported in some patients taking bisphosphonates.

"Denosumab is an important new therapy to prevent painful fractures in prostate cancer survivors," Smith says. "An ongoing clinical trial will also evaluate whether denosumab prevents spread of prostate cancer to bone, the most common site of metastases in men with this disease." Smith is an associate professor of Medicine at Harvard Medical School.

Along with the Amgen grant, the study received support from the National Institutes of Health and the Prostate Cancer Foundation. Additional co-authors of the NEJM article include Benjamin Leder, MD, MGH Endocrinology; Blair Egerdie, MD, Urology Associates, Kitchener, Ontario; Narciso Hernandez Toriz, MD; Centro Medico Nacional Siglo XXI, Mexico City; Robert Feldman, MD, Connecticut Clinical Research Center, Middlebury; Tuevo Tammela, MD, Tempere University Hospital, Finland; Fred Saad, MD, Central Hospital of the University of Montreal; Jiri Heracek, MD, PhD, Androgeos, Prague, Czech Republic; Maciej Szwedowski, MD, Wojewodzkie Centrum Medyczne, Opole, Poland; and Chunlei Ke, PhD, Amy Kupic, MA, and Carsten Goessl, MD, Amgen, Inc.

Massachusetts General Hospital, established in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $500 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, systems biology, transplantation biology and photomedicine.

denosumab一项癌症骨转移3期试验获疗效肯定结果

Ａｍｇｅｎ公司表示ｄｅｎｏｓｕｍａｂ在一项与Ｚｏｍｅｔａ（唑来膦酸）对比的３期试验中获得了肯定结果，这项试验考察ｄｅｎｏｓｕｍａｂ对于癌症骨转移患者的作用，这项试验有１７７６名晚期实体癌（不包括乳腺癌与前列腺癌）与多发性骨髓瘤患者参加。

试验证明使用ｄｅｎｏｓｕｍａｂ的患者发生首次骨相关事件的时间与使用Ｚｏｍｅｔａ的患者有可比性，说明ｄｅｎｏｓｕｍａｂ有效性不劣于Ｚｏｍｅｔａ。公司原计划要证明该药作用强于Ｚｏｍｅｔａ，但是没有达到此试验终点。还好试验中Ｚｏｍｅｔａ的副作用也不大于Ｚｏｍｅｔａ，并没有因为使用剂量比用于骨质疏松时大而出现并发症。

公司表示此数据可作为上市申报材料，公司计划在明年寻求该药用于癌症骨转移，目前该药已在美国申请用于治疗骨质疏松