A randomized, placebo-controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma
A randomized, placebo-controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma
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DOI：
10.1093/jnci/94.19.1458
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发表时间：
2002-10-02
影响因子：
10.3
通讯作者：
Chen, B
中科院分区：
文献类型：
--
作者：
Saad, F;Gleason, DM;Chen, B
背景：骨转移是前列腺癌患者发病的常见原因。我们研究了一种新的双膦酸盐，唑来膦酸，它可以阻止骨破坏，对前列腺癌骨转移患者的骨骼并发症的影响。研究方法：有骨转移病史的难治性前列腺癌患者被随机分配至双盲治疗方案：静脉注射唑来膦酸4 mg（N = 214）、唑来膦酸8 mg（随后减至4 mg; 8/4）（N = 221）或安慰剂（N = 208），每3周一次，持续15个月。评估了发生脊柱相关事件的患者比例、至首次发生脊柱相关事件的时间、骨骼发病率、疼痛和镇痛评分、疾病进展和安全性。所有统计学检验均为双侧检验。结果如下：大约38%接受唑来膦酸4 mg的患者、28%接受唑来膦酸8/4 mg的患者和31%接受安慰剂的患者完成了研究。接受安慰剂治疗的患者发生泌尿系统相关事件的比例高于接受唑来膦酸4 mg治疗的患者（44.2% vs 33.2%;差异=-11.0%，95%置信区间[CI] = -20.3%至-1.8%; P =.021）或接受唑来膦酸8/4 mg治疗的患者（38.5%;与安慰剂相比的差异=-5.8%，95%CI = -15.1%至3.6%; P = 0.222）。接受安慰剂治疗的患者的至首次脑卒中相关事件的中位时间为321天，接受唑来膦酸4 mg治疗的患者未达到（P = 0.011 vs安慰剂），接受唑来膦酸8/4 mg治疗的患者为363天（P = 0.491 vs安慰剂）。与接受安慰剂治疗的患者相比，接受唑来膦酸治疗的患者的尿骨吸收标志物在统计学上显著降低（P = 0.001）。接受安慰剂的患者的疼痛和镇痛评分比接受唑来膦酸的患者增加得更多，但各组之间的疾病进展、体力状态或生活质量评分没有差异。唑来膦酸4 mg 15分钟输注耐受性良好，但8 mg剂量与肾功能恶化相关。结论：唑来膦酸4 mg可减少前列腺癌骨转移患者的肿瘤相关事件。
Background: Bone metastases are a common cause of morbidity in patients with prostate carcinoma. We studied the effect of a new bisphosphonate, zoledronic acid, which blocks bone destruction, on skeletal complications in prostate cancer patients with bone metastases. Methods: Patients with hormone-refractory prostate cancer and a history of bone metastases were randomly assigned to a double-blind treatment regimen of intravenous zoledronic acid at 4 mg (N = 214), zoledronic acid at 8 mg (subsequently reduced to 4 mg; 8/4) (N = 221), or placebo (N = 208) every 3 weeks for 15 months. Proportions of patients with skeletal-related events, time to the first skeletal-related event, skeletal morbidity rate, pain and analgesic scores, disease progression, and safety were assessed. All statistical tests were two-sided. Results: Approximately 38% of patients who received zoledronic acid at 4 mg, 28% who received zoledronic acid at 8/4 mg, and 31% who received placebo completed the study. A greater proportion of patients who received placebo had skeletal-related events than those who received zoledronic acid at 4 mg (44.2% versus 33.2%; difference = -11.0%, 95% confidence interval [CI] = -20.3% to -1.8%; P =.021) or those who received zoledronic acid at 8/4 mg (38.5%; difference versus placebo = -5.8%, 95% CI = -15.1% to 3.6%; P =.222). Median time to first skeletal-related event "as 321 days for patients who received placebo, was not reached for patients who received zoledronic acid at 4 mg (P =.011 versus placebo), and was 363 days for those who received zoledronic acid at 8/4 mg (P =.491 versus placebo). Compared with urinary markers in patients who received placebo, urinary markers of bone resorption were statistically significantly decreased in patients who received zoledronic acid at either dose (P =.001). Pain and analgesic scores increased more in patients who received placebo than in patients who received zoledronic acid, but there were no differences in disease progression, performance status, or quality-of-life scores among the groups. Zoledronic acid at 4 mg given as a 15-minute infusion was well tolerated, but the 8-mg dose was associated with renal function deterioration. Conclusion: Zoledronic acid at 4 mg reduced skeletal-related events in prostate cancer patients with bone metastases.