Ernst D S, MacDonald R N, Paterson A H, Jensen J, Brasher P, Bruera E
J Pain Symptom Manage. 1992 Jan;7(1):4-11. doi: 10.1016/0885-3924(92)90101-m.
After a baseline symptom and laboratory assessment, 24 patients with metastatic bone disease and pain were randomized to receive either a 4-hr intravenous infusion of 2-dichloromethylene bisphosphonate (Cl2MDP), 600 mg in 500 mL of normal saline, or a 4-hr placebo infusion, 500 mL of normal saline. The administration was double blind. After 1 wk, the assessment was repeated and the patients were crossed over to the alternate treatment. After 1 more wk, a final assessment and blinded choice by the patient and investigator took place. Of the 21 evaluable patients, 12 (57%) chose the Cl2MDP and 4 (19%) chose the placebo; 5 (24%) patients did not have a specific preference (p = NS). The investigator chose the Cl2MDP in 14 (67%) cases, placebo in 6 (29%) cases and was unable to discern a difference in 1 (5%) case (p less than 0.05). The patients and investigator made similar selections in 16 (76%) instances. On the visual analogue scale assessments, a significant decrease in pain scores was observed following the Cl2MDP infusion (p less than 0.01) and an increase in activity scores was also demonstrated (p less than 0.01). No significant difference in the daily oral morphine equivalent analgesic requirement was demonstrated for either arm. No difference in clinical and laboratory parameters of toxicity was evident between the placebo and Cl2MDP arms of the trial. Our preliminary findings suggest that Cl2MDP is safe, and has analgesic properties that may prove to be useful in the management of metastatic bone pain.
在进行基线症状和实验室评估后，24例患有转移性骨病且伴有疼痛的患者被随机分为两组，一组接受4小时静脉输注2-二氯亚甲基双膦酸盐（Cl2MDP），600毫克溶于500毫升生理盐水中，另一组接受4小时安慰剂输注，即500毫升生理盐水。给药采用双盲方式。1周后，重复进行评估，患者交叉接受另一种治疗。再过1周后，进行最终评估，并由患者和研究者进行盲法选择。在21例可评估患者中，12例（57%）选择了Cl2MDP，4例（19%）选择了安慰剂；5例（24%）患者没有特定偏好（p=无显著性差异）。研究者在14例（67%）病例中选择了Cl2MDP，6例（29%）病例中选择了安慰剂，1例（5%）病例无法辨别差异（p<0.05）。患者和研究者在16例（76%）情况下做出了相似的选择。在视觉模拟量表评估中，输注Cl2MDP后疼痛评分显著降低（p<0.01），活动评分也有所提高（p<0.01）。两组的每日口服吗啡等效镇痛需求量均无显著差异。试验的安慰剂组和Cl2MDP组在临床和实验室毒性参数方面没有明显差异。我们的初步研究结果表明，Cl2MDP是安全的，并且具有镇痛特性，可能在转移性骨痛的治疗中有用。
