注射用钐乙二胺四甲基膦酸盐单剂量Ⅰ期临床研究

 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）。

A Phase Ⅰ Trial for Evaluating the Tolerance of Samarium-Ethylenedia Minertetra Methylene Phosphonic Acid

OBJECTIVE To evaluating the tolerance dose of samarium-ethylenedia minertetra methylene phosphonic acid( Sm-EDTMP )for the painful cancer patients who had bone metastasis. METHODS There were 4 dose group for 13 patients with metastatic bone tumor. They are two vials, three vials, four vials and five vials. 12 patients were evaluated for efficacy, 13 patients were evaluated for safety.Every patients were evaluated for pain,blood test and EKG during the study. RESULTS One patient belonging to four vials dose died because of disease progression.Twelve patients didn't undergo any adverse events.All patients belonging to two vials dose group had complete response or partial response. There was one inefficiency patient in the other three vials dose group.The pain evaluating score of the four vials were the highest. CONCLUSION The tolerance of four vials dose group were very well without Ⅳ grade hematologic toxicity and more than Ⅲ grade non-hematologic toxicity.The four vials dose group is more effective than the other dose group. So we recommended the phase Ⅱ study dose was four vials.