Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study

医学 德诺苏马布 唑来膦酸 前列腺癌 临床终点 内科学 肿瘤科 安慰剂 泌尿科 癌症 随机对照试验 骨质疏松症 病理 替代医学
作者
Karim Fizazi,Michael A. Carducci,Matthew R. Smith,Ronaldo Damião,Janet E. Brown,Lawrence I. Karsh,Piotr Milecki,Neal D. Shore,Michael Rader,Huei Wang,Qi Jiang,Sylvia Tadros,Roger Dansey,Carsten Goessl
出处
期刊:The Lancet [Elsevier BV]
卷期号:377 (9768): 813-822 被引量:1889
标识
DOI:10.1016/s0140-6736(10)62344-6
摘要

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.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 stratified by previous skeletal-related event, prostate-specific 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 first on-study skeletal-related 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. Efficacy analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00321620, and has been completed.1904 patients were randomised, of whom 950 assigned to denosumab and 951 assigned to receive zoledronic acid were eligible for the efficacy 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 first 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).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.Amgen.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
大力信封发布了新的文献求助10
刚刚
刚刚
元谷雪完成签到,获得积分10
1秒前
1秒前
2秒前
yiren发布了新的文献求助10
2秒前
LEE完成签到,获得积分10
2秒前
田様应助清新的冰凡采纳,获得10
2秒前
maybe完成签到,获得积分10
2秒前
dypdyp应助飞云采纳,获得10
3秒前
Dritsw应助超爱蛋炒饭采纳,获得10
3秒前
326361887完成签到,获得积分20
5秒前
吴昱晟发布了新的文献求助30
5秒前
崛起之邦完成签到,获得积分10
6秒前
学术的刘完成签到,获得积分10
6秒前
WPY完成签到,获得积分10
6秒前
无名发布了新的文献求助10
7秒前
可可发布了新的文献求助10
7秒前
小熊发布了新的文献求助10
7秒前
早安发布了新的文献求助10
9秒前
古拉桑发布了新的文献求助30
9秒前
大剑日太刀完成签到,获得积分10
10秒前
万能图书馆应助silvery采纳,获得10
10秒前
10秒前
12秒前
Cashwa完成签到,获得积分10
13秒前
13秒前
务实蜻蜓完成签到,获得积分10
13秒前
上官若男应助无名采纳,获得10
13秒前
小熊完成签到,获得积分20
13秒前
王小贝完成签到,获得积分10
13秒前
崛起之邦发布了新的文献求助10
14秒前
1351567822应助wang采纳,获得10
14秒前
YamDaamCaa应助cxzdm采纳,获得30
15秒前
15秒前
garey完成签到,获得积分20
15秒前
调皮铸海完成签到,获得积分10
15秒前
早安完成签到,获得积分10
17秒前
17秒前
18秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
Cognitive Neuroscience: The Biology of the Mind 1000
Technical Brochure TB 814: LPIT applications in HV gas insulated switchgear 1000
Toward a Combinatorial Approach for the Prediction of IgG Half-Life and Clearance 500
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
Picture Books with Same-sex Parented Families: Unintentional Censorship 500
Nucleophilic substitution in azasydnone-modified dinitroanisoles 500
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3970120
求助须知:如何正确求助?哪些是违规求助? 3514810
关于积分的说明 11176124
捐赠科研通 3250136
什么是DOI,文献DOI怎么找? 1795198
邀请新用户注册赠送积分活动 875647
科研通“疑难数据库(出版商)”最低求助积分说明 804964