沙尔威辛治疗恶性肿瘤I期临床耐受性试验

Phase I clinical trial of salvicine in patients with solid tumors

目的:观察沙尔威辛治疗恶性肿瘤的安全性,毒副反应与剂量的关系,确定推荐Ⅱ期临床研究的剂量。方法:共入选29例患者,沙尔威辛分为9个剂量组,由初始剂量15 mg.m-2.d-1开始逐渐增加至30,45,60,75,90,105 mg.m-2.d-1,加入生理氯化钠溶液500 mL静脉点滴2 h,连续3 d,其中第7剂量组为90 mg.m-2.d-1连续4 d,第8剂量组为90 mg.m-2.d-1连续5 d,第9剂量组为105 mg.m-2.d-1连续5 d,21 d为一周期,每剂量组3或4例。观察药物对人体各系统的影响及毒性反应。结果:沙尔威辛的毒副反应比较轻微,除了血管刺激疼痛外主要还包括Ⅰ/Ⅱ度的骨髓抑制、消化道反应、发热及皮肤潮红等,所有的毒副反应均在停药2周内恢复。没有出现剂量限制性毒性。爬坡最高剂量为105 mg.m-2.d-1连续5 d。结论:沙尔威辛对恶性肿瘤患者的耐受性良好,建议Ⅱ期临床研究推荐剂量为90 mg.m-2.d-1连续5 d,21 d为一周期。

Objective： To evaluate the safety and maximum tolerated dose of salvicine in patients with malignant tumors. Methods： 29 malignant cancer patients were recruited in the study. Cohorts of three or four patients were accrued to nine dosing of salvicine at 15, 30,45,60,75,90 mg·m^-2·d^- 1continuous 3 days, 90 mg·m^- 2·d^-1 continuous 4 days, 90 and 105 mg·m^- 2·d^-1 continuous 5 days for a 21 days course of chemotherapy to establish the maximum tolerated dose（MTD）. Results： Adverse reaction of salvicine were mild and tolerated. Besides stimulation of blood vessal, there were grade Ⅰ /Ⅱ adverse reactions including myelosuppression, GI dysfunction,fever and erubescence and so on. No dose limiting toxicity（ DLT） and no MTD were found in the study. The highest escalation dose was 105 mg·m^-2·d^-1 continuous 5 days. Conclusion： Salvicine was well tolerated in patients with solid tumors. The dosing regimen recommended in the phase I1 clinical trail was 90 mg·m^-2·d^-1 continuous 5 days.