Hirsh Vera, Tchekmedyian N Simon, Rosen Lee S, Zheng Ming, Hei Yong-Jiang
McGill University, Montreal, Quebec, Canada.
Clin Lung Cancer. 2004 Nov;6(3):170-4. doi: 10.3816/CLC.2004.n.030.
The results of a retrospective exploratory analysis of a phase III trial of zoledronic acid in patients with bone metastases secondary to lung cancer or other solid tumors are reported herein to assess the risk of skeletal-related events (SREs) and the efficacy of 4 mg zoledronic acid compared with placebo. The study is based on patient SRE history before study entry. Patients were stratified based on SRE history (eg, pathologic fracture, spinal cord compression, radiation therapy or surgery to bone, or hypercalcemia) before study entry, and SRE incidence over 21 months was analyzed. Of 507 patients randomized to 4 mg zoledronic acid or placebo, 131 completed the 9-month core phase and 69 entered the 12-month extension phase. Before study entry, 347 of 503 patients who were evaluable for efficacy (69%) experienced >/= 1 SRE; these patients had a higher risk of developing an SRE on study than patients with no prior SRE (odds ratio, 1.41). Among patients with an SRE before study entry, zoledronic acid reduced the risk of SREs by 31% (P = 0.009), reduced the mean skeletal morbidity rate (1.96 vs. 2.81 SREs per year for placebo; P = 0.030), and prolonged the median time to first SRE by nearly 4 months (215 days vs. 106 days for placebo; P = 0.011). Among patients with no SRE before study entry (n = 156), zoledronic acid reduced the risk of SREs by 23% (P = 0.308), reduced the mean skeletal morbidity rate (1.34 vs. 2.53 SREs per year for placebo; P = 0.332), and prolonged the median time to first SRE by 2.5 months (P = 0.534). This exploratory analysis demonstrates that patients with a history of SREs are at high risk for subsequent SREs, but zoledronic acid reduces skeletal morbidity regardless of SRE history.
本文报告了一项针对肺癌或其他实体瘤骨转移患者的唑来膦酸III期试验的回顾性探索性分析结果,以评估骨相关事件(SREs)的风险以及4mg唑来膦酸与安慰剂相比的疗效。该研究基于患者入组前的SRE病史。患者根据入组前的SRE病史(如病理性骨折、脊髓压迫、骨放疗或手术、或高钙血症)进行分层,并分析21个月内的SRE发生率。在随机接受4mg唑来膦酸或安慰剂的507例患者中,131例完成了9个月的核心阶段,69例进入了12个月的延长期。入组前,503例可评估疗效的患者中有347例(69%)经历过≥1次SRE;这些患者在研究中发生SRE的风险高于无既往SRE的患者(优势比,1.41)。在入组前有SRE的患者中,唑来膦酸使SRE风险降低了31%(P = 0.009),降低了平均骨发病率(安慰剂组为每年1.96次与2.81次SRE;P = 0.030),并使首次发生SRE的中位时间延长了近4个月(安慰剂组为215天与106天;P = 0.011)。在入组前无SRE的患者中(n = 156),唑来膦酸使SRE风险降低了23%(P = 0.308),降低了平均骨发病率(安慰剂组为每年1.34次与2.53次SRE;P = 0.332),并使首次发生SRE的中位时间延长了2.5个月(P = 0.534)。这项探索性分析表明,有SRE病史的患者后续发生SRE的风险较高,但无论SRE病史如何,唑来膦酸均可降低骨发病率。