Berman E, Raymond V, Daghestani A, Arlin Z A, Gee T S, Kempin S, Hancock C, Williams L, Stevens Y W, Clarkson B D
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York.
Cancer Res. 1989 Jan 15;49(2):477-81.
We conducted a Phase I-II trial of 4-demethoxydaunorubicin (idarubicin, IDR) in combination with 1-beta-D-arabinofuranosylcytosine (ara-C) in 51 patients with relapsed or refractory acute nonlymphocytic leukemia, acute lymphocytic leukemia, or chronic myelogenous leukemia in blast crisis. Only 1 of 12 patients treated at the first dose level (idarubicin, 10 mg/m2/day for 3 days and ara-C, 25 mg/m2 i.v. bolus followed by 200 mg/m2 continuous infusion daily for 5 days) achieved aplasia and complete remission. The dose of idarubicin was subsequently increased to 10 mg/m2/day for 4 days with the ara-C dose held constant. Complete remission incidence for this dose schedule was: 7 of 31 patients with acute nonlymphocytic leukemia, 0 of 5 patients with acute lymphocytic leukemia, 0 of 1 patient with chronic myelogenous leukemia in blast crisis, and 1 of 2 patients with biphenotypic leukemia. Nonhematological toxicity included nausea, vomiting, mucositis, and abnormal liver function tests. Detailed pharmacological studies were performed to determine whether ara-C altered IDR metabolism or that of its main metabolite, 13-hydroxyidarubicinol or IDR clearance. A high degree of variability among patients was apparent and no consistent effect could be demonstrated. In summary, 9 of 37 patients (24%) with relapsed or refractory ANLL, including 1 patient with biphenotypic leukemia, achieved remission. We conclude that idarubicin in combination with ara-C is an active combination in patients with relapsed or refractory leukemia.
我们对51例复发或难治性急性非淋巴细胞白血病、急性淋巴细胞白血病或慢性粒细胞白血病急变期患者进行了一项4-去甲氧柔红霉素（伊达比星，IDR）联合1-β-D-阿拉伯呋喃糖基胞嘧啶（阿糖胞苷，ara-C）的I-II期试验。在第一剂量水平治疗的12例患者中（伊达比星，10mg/m²/天，共3天，阿糖胞苷，25mg/m²静脉推注，随后200mg/m²持续输注，每天1次，共5天），只有1例出现再生障碍和完全缓解。随后伊达比星剂量增加至10mg/m²/天，共4天，阿糖胞苷剂量保持不变。该剂量方案的完全缓解发生率为：31例急性非淋巴细胞白血病患者中有7例，5例急性淋巴细胞白血病患者中无1例，1例慢性粒细胞白血病急变期患者中无1例，2例双表型白血病患者中有1例。非血液学毒性包括恶心、呕吐、粘膜炎和肝功能检查异常。进行了详细的药理学研究，以确定阿糖胞苷是否改变了伊达比星的代谢或其主要代谢产物13-羟基伊达比星醇的代谢或伊达比星的清除率。患者之间存在高度变异性，未发现一致的效应。总之，37例复发或难治性急性非淋巴细胞白血病患者中有9例（24%），包括1例双表型白血病患者，实现了缓解。我们得出结论，伊达比星联合阿糖胞苷对复发或难治性白血病患者是一种有效的联合治疗方案。
