唑来膦酸治疗实体瘤或多发性骨髓瘤骨转移所致疼痛的Ⅲ期临床研究

[Phase III clinical study of zoledronic acid in the treatment of pain induced by bone metastasis from solid tumor or multiple myeloma].

作者信息

Dong Mei, Feng Feng-Yi, Zhang Yang, Xie Guang-Ru, Wang Ya-Jie, Liu Ji-Wei, Song San-Tai, Zhou Qing-Hua, Ren Jun, Jiao Shun-Chang, Li Jin, Wang Xiu-Wen, Chen Qiang, Wang Zhe-Hai, Xu Nong, Feng Ji-Feng

机构信息

Department of Medical Oncology, Cancer Hospital (Institute), Chinese Academy of Medical Sciences, Beijing 100021, China.

出版信息

Zhonghua Zhong Liu Za Zhi. 2008 Mar;30(3):215-20.

PMID:18756940

Abstract

OBJECTIVE

To evaluate the efficacy and safety of zoledronic acid in the treatment of bone pain in patients with bone metastasis from solid tumor or multiple myeloma.

METHODS

A randomized, double-blind, double-simulated and multi-center phase III clinical trail with pamidronate as control was conducted. Patients with moderate to severe bone pain (VAS > 50 mm) induced by solid tumor or multiple myeloma were randomized to receive intravenous zoledronic acid 4 mg or pamidronate 90 mg. Then the change of VAS and urinary NTX/Cr and CTX/Cr were observed in two groups.

RESULTS

From July 2005 to September 2006, 228 patients with bone pain induced by bone metastasis from 15 cancer centers were randomize into two groups: 116 patients in zoledronic acid group and 112 patients in pamidronate group. The VAS value was decreased gradually after treatment in these two groups. Significant improvement in bone pain after treatment were observed both in zoledronic acid group and the control group when compared with baseline VAS on D8 (-11.77% vs. -10.87%), D15 (-24.60% vs. -21.06%) and D28 (-32.37% vs. -31.26%) (P< or =0.0001), but no significant difference existed between two groups (P =0.6587). Compared with baseline, urine NTX/Cr and CTX/Cr level were decreased rapidly after treatment in both groups, the nadir was on D8, the median decreased on D28, which was -36.9% vs. -32.1% for NTX/Cr (P = 0.7922) and -63.2% vs. -47.9% for CTX/Cr (P =0.834). The frequently observed adverse events were pyrexia (19.0% vs. 31.3%), vomiting (6.0% vs. 8.9%), nausea (4.3% vs. 4.5%), fatigue (3.4% vs. 2.7%) and constipation (2.6% vs. 1.8%) in the two groups. Compared with baseline, the serum creatinine level was not significantly increased throughout the study.

CONCLUSION

Intravenous injection of 4 mg zoledronic acid can significantly reduce bone pain and bone resorption marker in urine in the Chinese patients with bone metastasis from solid tumor or multiple myeloma, which is tolerable and also comparable to pamidronate in the efficacy and safety.

摘要

目的

评估唑来膦酸治疗实体瘤或多发性骨髓瘤骨转移患者骨痛的疗效和安全性。

方法

进行一项以帕米膦酸为对照的随机、双盲、双模拟、多中心III期临床试验。将实体瘤或多发性骨髓瘤引起的中重度骨痛（视觉模拟评分法[VAS]>50 mm）患者随机分为两组，分别静脉注射4 mg唑来膦酸或90 mg帕米膦酸。然后观察两组患者VAS、尿NTX/Cr和CTX/Cr的变化。

结果

2005年7月至2006年9月，来自15个癌症中心的228例骨转移引起骨痛的患者被随机分为两组：唑来膦酸组116例，帕米膦酸组112例。两组治疗后VAS值均逐渐下降。与基线VAS相比，唑来膦酸组和对照组在第8天（-11.77%对-10.87%）、第15天（-24.60%对-21.06%）和第28天（-32.37%对-31.26%）骨痛均有显著改善（P≤0.0001），但两组间无显著差异（P =0.6587）。与基线相比，两组治疗后尿NTX/Cr和CTX/Cr水平迅速下降，最低点在第8天，第28天中位数下降，NTX/Cr分别为-36.9%对-32.1%（P = 0.7922），CTX/Cr分别为-63.2%对-47.9%（P =0.834）。两组常见的不良事件有发热（19.0%对31.3%）、呕吐（6.0%对8.9%）、恶心（4.3%对4.5%）、疲劳（3.4%对2.7%）和便秘（2.6%对1.8%）。在整个研究过程中，与基线相比，血清肌酐水平无显著升高。