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目的对注射用钐乙二胺四亚甲基膦酸盐(Sm-EDTMP)治疗癌症骨转移疼痛的临床研究,补做单次剂量耐受性试验,探索更好的安全有效剂量,提供与安慰剂进行对照研究的剂量依据。方法研究共进行了4个剂量组,分别是2、3、4和5支。总计13例患者,有12例可以评价疗效,13例可以评价不良反应。每例患者给药前后进行疼痛评分评价,并进行血常规、血生化、心电图等安全性检查。结果 13例入组患者仅4支剂量组有1例出现严重不良事件——死亡,原因是病情进展,与研究药物无关。余12例患者无其他不良事件发生。2支剂量组患者全部有效,而3、4和5支剂量组各有1例患者无效。4支剂量组无论是疗前疼痛最高分、疼痛最低分和爆发痛次数中位值均是4个剂量组最高的,而其有效比率却与3和5支剂量组是相同的。4支剂量组达PR患者的时间仅为2 d,起效很快,维持时间较长可达27 d。结论 4个剂量组均耐受性良好,未观察到Ⅳ度血液学毒性和≥Ⅲ度的非血液学毒性。根据现有的疗效结果,4支剂量组疼痛最高分、疼痛最低分和爆发痛次数的平均值和中位值均是最高的,疗效略低于2支剂量组,但与3、5支剂量组相同。同时从疼痛评分变化和爆发痛变化时间曲线上看到,对疼痛最高分和爆发痛次数的控制,4支剂量组更好。在未来进行的Ⅱ期临床研究中,推荐剂量是4支Sm-EDTMP(相当EDTMP 268 mg)。
Objective To study the clinical study of inosine ethylenediaminetetramethylenephosphonate (Sm-EDTMP) for the treatment of bone metastasis pain in cancer, make up a single dose tolerance test, explore better safe and effective dose, provide and comfort Dosage bases for controlled studies. Methods A total of four dose groups were studied, 2, 3, 4 and 5, respectively. A total of 13 patients, 12 cases can evaluate the efficacy, 13 cases can evaluate adverse reactions. Each patient was evaluated for pain scores before and after administration, and blood safety, blood biochemistry, and electrocardiogram were performed. Results One of the 13 patients in the 4 dose group had serious adverse events--death due to the progression of the disease, which was not related to the study drug. There were no other adverse events in the remaining 12 patients. All patients in the 2 dose group were effective, while 1 in 3, 4 and 5 dose groups were all ineffective. The median scores of the highest pain scores, lowest pain scores, and burst pain scores in the 4 dose groups were the highest in the 4 dose groups, while the effective rates were the same as those in the 3 and 5 dose groups. The time for PR patients in the 4 dose group was only 2 days, and the onset was rapid, with a long duration of up to 27 days. Conclusion The four dose groups were well tolerated, and no IV hematologic toxicity and non-hematological toxicity of ≥ III degrees were observed. According to the existing efficacy results, the average and median values of the highest pain score, lowest pain score, and number of outbreak pains in the 4 dose groups were the highest, and the efficacy was slightly lower than that of the 2 dose groups, but with 3 and 5 doses The same group. At the same time, it can be seen from the time curve of pain score changes and burst pain changes that the control of the highest pain scores and burst pain times is better in the 4 dose group. In a future Phase II clinical study, the recommended dose is 4 Sm-EDTMPs (equivalent to EDTMP 268 mg).