注射用唑来膦酸对恶性肿瘤骨转移疼痛的临床疗效和安全性分析

Zoledronic acid in the treatment of malignancy patients with bone metastases: A study of clinical effect and safety

目的:评价注射用唑来膦酸治疗肿瘤骨转移引起疼痛的有效性及安全性。方法:50例癌症骨转移中度以上疼痛患者随机、双盲和双模拟分为两组,每组25例。研究组为唑来膦酸4 mg加入生理盐水注射液100 mL中静脉滴入15 min;对照组为帕米膦酸二钠60 mg加入5%葡萄糖或生理盐水注射液500 mL中静脉滴入至少4 h。对治疗前、治疗后第7天和第14天的NRS、QOL、KPS、缓解率和加用止痛剂情况进行比较;同时,对药物的不良事件、血尿常规和生化等指标进行评估。结果:治疗前研究组和对照组具有可比性。治疗后两组的NRS较治疗前明显降低(治疗前、治疗后第7天和第14天:研究组6.36vs4.08vs3.28,P<0.01;对照组5.92vs4.20vs3.36,P<0.01),具有明显缓解疼痛的作用;治疗后两组的QOL较治疗前明显提高(治疗前、治疗后第7天和第14天:研究组18.92vs23.40vs24.20,P<0.01;对照组19.56vs23.12vs23.88,P<0.01),明显改善了生活质量,治疗后两组的KPS较治疗前也明显改善(治疗前和治疗后第14天:研究组67.60vs78.00,P<0.01;对照组60.80vs70.80,P<0.01),但治疗后两组间差异均无统计学意义。疼痛总缓解率研究组稍高于对照组,但差异无统计学意义(第7天60%vs48%,P=0.395;第14天80%vs72%,P=0.742);加服即释吗啡人数研究组和对照组各1例。对照组中有1例在输注帕米膦酸后出现轻度全身疼痛,约12 h后自行消失。结论:唑来膦酸对癌症骨转移的疼痛有良好的疗效,且具有给药时间短、给药剂量小和作用时间长的临床特点。不良反应轻微,患者耐受良好。

OBJECTIVE：To evaluate the effectiveness and safety of zoledronic acid in the treatment of pain caused by bone metastases. METHODS： Fifty patients with pain over moderate level caused by meta were randomizedy devided two groups stic bone tumor into the study group received 4 mg zoledronic acid infusion for 15 minutes or and the control group received 60 mg pamidronate infusion for 4 hours. The primary effective parameters were pain scores, quality of life, KPS score and pain relief rates. The vital signs, biochemical and hematological parameters were determined. All patients provided a written informed consent. RESULTS： Pain scores were significantly lower after 7 and 14 days treatment in both groups （study group 6. 36 vs 4. 08 vs 3. 28, P^0. 01, control group 5. 92 vs 4. 20 vs 3.36,P〈0. 01）. Quality of life also improved in both groups （study group 18. 92 vs 23. 40 vs 24. 20, P%O. 01, control group 19.56 vs 23. 12 vs 23. 88, P〈 0. 01）. KPS scores on 14th day post-infusion were significantly different from those before in two groups （study group 67. 60 vs 78. 00,P〈0. 01, control group 60. 80 vs 70. 80, P〈0. 01）. There was no statistical significance of difference between two groups on all primary effective parameters. The pain relief rate （CR＋PR） was 80% in the study group and 72% in the control group at the end point, P=0. 742. Each group registered one additive analgetic using. Compared with pamidronate, zoledronic acid was infused in much shorter time and less dose. An adverse event of mild systemic skeletal pain was recorded after pamidronate infusion and completely reversed after 12 hours. CONCLUSlONS： As a supplement to therapy antincoplastic, zoledronic showed has similar effectiveness with pamidronate and is well tolerated in relieving pain of malignant tumor with metastatic bone tumor. It also provided a distinct advantage for patients and nursing.