马来酸氨柔比星Ⅰ期临床耐受性研究

A phase Ⅰ clinical tolerance trial for maleate amrubicin

目的:确定马来酸氨柔比星静脉给药在人体的剂量限制性毒性(DLT)及最大耐受剂量(MTD);初步观察其对晚期实体瘤患者的疗效。方法:单次给药设60,70,75,80,90,100和110 mg.m-27个剂量组;多次给药设25,30,35和38 mg.m-24个剂量组。单次给药为d 1给药,多次给药为d 1～d 3给药,21 d重复。2周期后评价疗效。结果:DLT为Ⅳ度骨髓抑制及Ⅲ度胃肠道反应。其他不良反应包括乏力、腹泻、头痛、心悸、心前区疼痛、黏膜炎等,均很轻微。2周期后4例患者为疾病部分缓解(PR),6例患者为病变稳定(SD)。结论:人体对马来酸氨柔比星耐受良好,晚期肿瘤患者中多次给药和单次给药的MTD分别是35和100 mg.m-2。初步观察到马来酸氨柔比星有广谱抗肿瘤活性,推荐Ⅱ期临床给药方式为单次给药100 mg.m-2,3周重复。

Objective： To determine the dose limited toxicities （DLT） and maximum tolerated dose （MTD）; To observe the effect of maleate amrubicin injected in patients with advanced solid tumors. Methods： 38 patients with advanced solid tumors were treated with maleate amrubicin intravenously at doses of 60, 70, 75, 80, 90, 100, 110 mg？m-2 on the first day or 25, 30, 35, 38 mg？m-2 on three consecutive days every 3 weeks. The efficacy was evaluated every 2 cycles. Results： The DLT was myelosuppression and gastrointestinal reaction. Other mild adverse events include fatigue, diarrhea, headache, palpitation, precordial pain and mucositis. 4 patients got PR and another 6 patients got SD at the end of 2 cycles. Conclusion： Maleate amrubicin was clinically tolerated well. The MTD was 100 and 35 mg？m-2 for single dose and multiple dose administration respectively. Maleate amrubicin was effective for multiple solid tumors. The dose of 100 mg？m-2 on the first day every 3 week in phase Ⅱ study is recommended.