注射用唑来膦酸治疗肺癌骨转移疼痛的疗效和安全性临床研究

Clinical Study on Effectiveness and Safety of Intravenous Zoledronic Acid for the Relief of Bone Pain in Patients with Advanced Lung Cancer

目的:探讨注射用唑来膦酸治疗肺癌骨转移引起疼痛的有效性及安全性。方法:对41例肺癌骨转移且中度以上疼痛患者进行前瞻、随机、双盲、双模拟平行临床研究,研究组21例,为注射用唑来膦酸4mg;对照组20例,为注射用帕米膦酸60mg。在研究期间两组均未进行任何化疗;对治疗前、治疗后第7天和第14天的主要有效指标NRS、缓解率和加用止痛剂及次要有效指标QOL、KPS情况进行比较,并分析不良事件发生和实验室指标异常情况。结果:组内比较:治疗后的NRS、QOL及KPS较治疗前均明显改善。组间比较:治疗后第14天研究组NRS明显低于对照组(3.38vs4.55,P<0.05),即治疗后第14天唑来膦酸缓解疼痛的作用明显优于帕米膦酸。疼痛总缓解率:研究组第7天57.1%、第14天61.9%;对照组分别为45%、50%,无统计学差异。在加服即释吗啡人数比较中:研究组1例,而对照组3例。不良事件比较:研究组1例,对照组4例,主要表现发烧、恶心呕吐(与输液较快有关,减慢输液速度后消失),不良事件与研究药物有关。结论:注射用唑来膦酸治疗肺癌骨转移疼痛疗效明显、具有良好的耐受性和安全性,且给药方便。

Objective： To compare the effectiveness and safety of zoledronic acid with pamidronate in advanced lung cancer patients with bone metastases. Methods： Forty-one patients with moderate to severe pain due to osteolytic metastases were assigned into a prospective, randomized, double-blind and double-dummy study. There were 21 patients in the experimental group who were treated with zoledronic acid （4mg/？）, and there were 20 patients in the control group who were treated with pamidronate （60mg/？）. The primary effective endpoints were pain scores （numerical rating scale, NRS）, pain relief rates and additive analgetic. The secondary efficacy parameters were quality of life （QOL） and Karnofsky performance status （KPS）. The vital signs and lab parameters were monitored. Results： Fourteen days after zoledronie acid or pamidronate infusion, NRS, QOL and KPS were significantly improved. Zoledronic acid significantly relieved pain compared with pamidronate （NRS： 3.38 vs 4.55, P〈0.05） at the end point. The pain relief rate was 61.9% for zoledronic acid and 50% for pamidronate （P〉0.05）. Morphine use was observed in one patient in the group receiving zoledronic acid and in three patients in the group receiving pamidronate. Zoledronic acid ameliorated QOL and KPS similarly to pamidronate. The infusion time of zoledronic acid was significantly shorter compared with pamidronate （15 min vs 4 hrs）. Adverse effects occurred in one patient in the zoledronic acid group and in four patients in the pamidronate group. The most common adverse effects included fever, nausea and vomiting. Conclusions： Zoledronic acid was more effective than pamidronate in palliating pain in advanced lung cancer patients with bone metastases. Zoledronic acid also provided a distinct convenience because of the short infusion time of 15 min compared with 4 hours for pamidronate infusion. Zoledronic acid and pamidronate were tolerated equally well.