Hiddemann W, Achterrath W, Urbanitz D, Preusser P, Balleisen L, Kirchhof B, Stenzinger W, Büchner T
Onkologie. 1984 Aug;7(4):214-6. doi: 10.1159/000215442.
In a phase I study the combination of AMSA and etoposide was applied to 12 patients with intensively pretreated, refractory AML to evaluate the basis for a subsequent phase II study in terms of drug dosage and timing. Each treatment cycle consisted in a 5-day regimen of AMSA 210 mg/m2/d days 2, 3 and 4. Etoposide was administered on days 1 and 5 with a constant loading dose of 100 mg/m2 by an 1-h infusion followed by a 23-h infusion, the dose of which was escalated in 3 steps from 110 mg/m2 to 200 mg/m2 and 230 mg/m2. In 18 treatment cycles the recommended dosage for a subsequent phase II study was found to be 660 mg/m2 etoposide per cycle together with 630 mg/m2 AMSA per course. Main side effects were nausea and vomiting as well as mucositis; 1 patient developed a severe intrahepatic cholestasis. In 11 from 16 evaluable treatment cycles a significant reduction of bone marrow blasts was observed with a mean cytoreduction rate of 0,26 log10/d. 4 patients, 3 of whom were primarily resistent to 2 TAD induction courses, achieved a partial remission.
在一项I期研究中，将氨茴环素（AMSA）和依托泊苷联合应用于12例经过强化预处理的难治性急性髓系白血病（AML）患者，以评估后续II期研究在药物剂量和给药时间方面的依据。每个治疗周期包括在第2、3和4天给予氨茴环素210mg/m²/d，共5天的方案。依托泊苷在第1天和第5天给药，初始负荷剂量为100mg/m²，静脉输注1小时，随后进行23小时输注，其剂量从110mg/m²分3步递增至200mg/m²和230mg/m²。在18个治疗周期中，发现后续II期研究的推荐剂量为每个周期依托泊苷660mg/m²，每个疗程氨茴环素630mg/m²。主要副作用为恶心、呕吐以及粘膜炎；1例患者出现严重的肝内胆汁淤积。在16个可评估的治疗周期中的11个周期观察到骨髓原始细胞显著减少，平均细胞减少率为0.26 log10/d。4例患者获得部分缓解，其中3例最初对2个三尖杉酯碱-阿糖胞苷-柔红霉素（TAD）诱导疗程耐药。
