Background Bone metastases are a major burden in men with advanced prostate cancer. We compared denosumab,
a human monoclonal antibody against RANKL, with zoledronic acid for prevention of skeletal-related events in
men with bone metastases from castration-resistant prostate cancer.
Methods In this phase 3 study, men with castration-resistant prostate cancer and no previous exposure to
intravenous bisphosphonate were enrolled from 342 centres in 39 countries. An interactive voice response system
was used to assign patients (1:1 ratio), according to a computer-generated randomisation sequence, to receive
120 mg subcutaneous denosumab plus intravenous placebo, or 4 mg intravenous zoledronic acid plus subcutaneous
placebo, every 4 weeks until the primary analysis cutoff date. Randomisation was stratifi ed by previous skeletalrelated
event, prostate-specifi c antigen concentration, and chemotherapy for prostate cancer within 6 weeks before
randomisation. Supplemental calcium and vitamin D were strongly recommended. Patients, study staff , and
investigators were masked to treatment assignment. The primary endpoint was time to fi rst on-study skeletalrelated
event (pathological fracture, radiation therapy, surgery to bone, or spinal cord compression), and was
assessed for non-inferiority. The same outcome was further assessed for superiority as a secondary endpoint.
Effi cacy analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00321620,
and has been completed.
Findings 1904 patients were randomised, of whom 950 assigned to denosumab and 951 assigned to receive
zoledronic acid were eligible for the effi cacy analysis. Median duration on study at primary analysis cutoff date was
12·2 months (IQR 5·9–18·5) for patients on denosumab and 11·2 months (IQR 5·6–17·4) for those on zoledronic
acid. Median time to fi rst on-study skeletal-related event was 20·7 months (95% CI 18·8–24·9) with denosumab
compared with 17·1 months (15·0–19·4) with zoledronic acid (hazard ratio 0·82, 95% CI 0·71–0·95; p=0·0002 for
non-inferiority; p=0·008 for superiority). Adverse events were recorded in 916 patients (97%) on denosumab and
918 patients (97%) on zoledronic acid, and serious adverse events were recorded in 594 patients (63%) on
denosumab and 568 patients (60%) on zoledronic acid. More events of hypocalcaemia occurred in the denosumab
group (121 [13%]) than in the zoledronic acid group (55 [6%]; p<0·0001). Osteonecrosis of the jaw occurred
infrequently (22 [2%] vs 12 [1%]; p=0·09).
Interpretation Denosumab was better than zoledronic acid for prevention of skeletal-related events, and potentially
represents a novel treatment option in men with bone metastases from castration-resistant prostate cancer.
2.pdf (840.18k) 在线查看 本人已认领以上摘要，48小时内完成。若超过时间，请其他站友自由认领 晚期乳腺癌的化学治疗及研究进展对骨转移灶也能起到治疗作用,而对激素类药物治疗有效的肿瘤,如乳腺癌、前列腺癌等应... 这些药物中最有希望的药物包括了安进公司的人源化单克隆抗体Denosumab,这种抗体能...cotmail.spaces.live.com/blog/-2004-03-27-快照-治疗及研究进展" 追踪 新进展文件类型:PDF/Adobe Acrobat- 文字版方双膦酸盐 渊Denosumab 或托瑞米芬冤 治疗遥 渊编译 关有彦冤 20- - PDF 文件使... 灵医药渊BSP冤肿瘤产品线将 在此基础上努力实现新分子 实体渊NME冤研究与生命周 ...www.mdweekly.cn/...zlkx/26.pdf-2011-02-14-[标签:content2]
作者:admin@医学,生命科学 2011-03-06 22:58