Possible survival benefits from zoledronic acid treatment in patients with bone metastases from solid tumours and poor prognostic features-An exploratory analysis of placebo-controlled trials.
Possible survival benefits from zoledronic acid treatment in patients with bone metastases from solid tumours and poor prognostic features-An exploratory analysis of placebo-controlled trials.
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DOI：
10.1016/j.jbo.2013.01.002
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发表时间：
2013-06
影响因子：
3.4
通讯作者：
Body JJ
中科院分区：
文献类型：
--
作者：
Coleman RE;Lipton A;Costa L;Cook RJ;Lee KA;Saad F;Brown JE;Terpos E;Major PP;Kohno N;Smith M;Body JJ
唑来膦酸（ZOL）是转移性骨病（MBD）患者治疗的重要组成部分，可降低患者发生肿瘤相关事件（SRE）的风险。我们评估了安慰剂对照ZOL试验中继发于实体瘤的MBD患者的总生存期（OS）。使用来自三项ZOL与安慰剂随机试验的数据库进行探索性分析。对1126例患者（ZOL组，n=731;安慰剂组，n=395）的OS进行了评估，这些患者具有18个预定义参数的完整基线数据。使用分层和校正的考克斯回归模型评估相对风险（RR）及其95%置信区间。定义ZOL治疗对OS具有显著不同影响的患者人群（通过逐步向后消除确定）的基线协变量纳入多变量模型。尽管总体治疗组之间的OS相似，但ZOL显著改善了基线NTX升高（≥100 nmol/mmol肌酐; RR，0.692; P=.0028）患者亚组（n=423; 38%）的OS。值得注意的是，这种效果是独立的SRE预防。与ZOL的OS获益相关的其他协变量（例如，低白蛋白、SRE病史、乳酸脱氢酶升高、癌症持续时间较短）是晚期疾病的特征。这些探索性分析表明，ZOL对高度侵袭性或晚期MBD患者的OS具有有益作用。
Zoledronic acid (ZOL) is an important component of therapy for patients with metastatic bone disease (MBD) to reduce the risk of skeletal-related events (SREs). We evaluated overall survival (OS) in patients with MBD secondary to solid tumours included in placebocontrolled ZOL trials. Exploratory analyses were performed using databases from three randomised trials of ZOL versus placebo. 1126 patients (ZOL, n=731; placebo, n=395) with complete baseline data for 18 predefined parameters were evaluated for OS. Relative risks (RRs) with 95% confidence intervals were assessed using stratified and adjusted Cox regression models. Baseline covariates defining patient populations with significantly different effects of ZOL treatment on OS (identified by stepwise backward elimination) were included in multivariate models. Although OS was similar between the overall treatment groups, ZOL significantly improved OS in the subset of patients (n=423; 38%) with elevated baseline NTX (≥100 nmol/mmol creatinine; RR, 0.692; P=.0028). Notably, this effect was independent of SRE prevention. Additional covariates associated with OS benefits with ZOL (e.g., low albumin, SRE history, elevated lactate dehydrogenase, shorter cancer duration) were characteristic of advanced disease. These exploratory analyses suggest a beneficial effect of ZOL on OS in patients with highly aggressive or advanced MBD.