Daghestani A N, Arlin Z A, Leyland-Jones B, Gee T S, Kempin S J, Mertelsmann R, Budman D, Schulman P, Baratz R, Williams L
Cancer Res. 1985 Mar;45(3):1408-12.
Fifty-two adults treated previously with either acute leukemia (43 patients) or blastic-phase chronic myelogenous leukemia (nine patients) received 4-demethoxydaunorubicin (20 to 45 mg/sq m) i.v. over 2 to 3 days. Three of the ten patients with acute lymphocytic leukemia achieved a complete remission (CR) lasting 5 to 7 weeks. Five of the 28 patients with acute nonlymphocytic leukemia achieved a CR lasting 5 to 80 weeks. All remissions were induced with one course of treatment with a median time to CR of 28 days (range, 22 to 40 days). None of the patients with blastic chronic myelogenous leukemia or secondary leukemia achieved a CR. The drug was well tolerated; mucositis (36%), nausea and vomiting (35%), and hepatic dysfunction (26%) were the most common side effects. Pharmacokinetic observations on five patients demonstrated multiphasic clearance of 4-demethoxydaunorubicin and extensive formation and prolonged retention of 4-demethoxy-13-hydroxydaunorubicin; that metabolite accumulated in plasma on repeated daily dosing. 4-Demethoxydaunorubicin has sufficient antileukemic activity in both acute lymphocytic leukemia and acute nonlymphocytic leukemia to warrant a prospective comparison, in combination regimens, against the conventional anthracyclines, daunorubicin and/or doxorubicin.
52名曾接受过急性白血病（43例）或慢性粒细胞白血病急变期（9例）治疗的成人患者，静脉注射4-去甲氧柔红霉素（20至45mg/平方米），持续2至3天。10例急性淋巴细胞白血病患者中有3例获得了持续5至7周的完全缓解（CR）。28例急性非淋巴细胞白血病患者中有5例获得了持续5至80周的CR。所有缓解均由一个疗程的治疗诱导产生，达到CR的中位时间为28天（范围为22至40天）。慢性粒细胞白血病急变期或继发性白血病患者均未达到CR。该药物耐受性良好；口腔炎（36%）、恶心和呕吐（35%）以及肝功能障碍（26%）是最常见的副作用。对5名患者的药代动力学观察表明，4-去甲氧柔红霉素具有多相清除特性，且4-去甲氧基-13-羟基柔红霉素形成广泛且潴留时间延长；该代谢产物在每日重复给药时会在血浆中蓄积。4-去甲氧柔红霉素在急性淋巴细胞白血病和急性非淋巴细胞白血病中均具有足够的抗白血病活性，值得在联合方案中与传统蒽环类药物柔红霉素和/或阿霉素进行前瞻性比较。
