Coleman Robert E, Lipton Allan, Costa Luis, Cook Richard J, Lee Ker-Ai, Saad Fred, Brown Janet E, Terpos Evangelos, Major Pierre P, Kohno Norio, Smith Matthew, Body Jean-Jacques
Department of Oncology, Cancer Clinical Trials Centre, University of Sheffield, Weston Park Hospital, Cancer Research Centre, Sheffield, UK.
College of Medicine, Penn State Milton S. Hershey Medical Center, Hershey, PA, USA.
J Bone Oncol. 2013 Feb 9;2(2):70-6. doi: 10.1016/j.jbo.2013.01.002. eCollection 2013 Jun.
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.
唑来膦酸（ZOL）是转移性骨病（MBD）患者治疗的重要组成部分，可降低骨相关事件（SREs）的风险。我们评估了在安慰剂对照的ZOL试验中纳入的实体瘤继发MBD患者的总生存期（OS）。
使用ZOL与安慰剂的三项随机试验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）进行了OS评估，这些患者具有18个预定义参数的完整基线数据。使用分层和调整的Cox回归模型评估95%置信区间的相对风险（RRs）。定义ZOL治疗对OS有显著不同影响的患者群体的基线协变量（通过逐步向后排除确定）纳入多变量模型。
尽管总体治疗组之间的OS相似，但ZOL在基线NTX升高（≥100 nmol/mmol肌酐；RR，0.692；P = 0.0028）的患者亚组（n = 423；38%）中显著改善了OS。值得注意的是，这种效果独立于SRE预防。与ZOL的OS获益相关的其他协变量（如低白蛋白、SRE病史、乳酸脱氢酶升高、癌症病程较短）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有有益作用。
