Moore J O, Olsen G A
Semin Oncol. 1984 Sep;11(3 Suppl 1):41-6.
Eleven academic institutions were selected to study mitoxantrone administered on a schedule of 10 mg/m2/d for five days initially and later at 12 mg/m2/d for five days, each given as a 30 minute intravenous (IV) infusion each day. Patients with acute or chronic leukemia were stratified by leukemic type and clinical status and included one group of patients considered to be in relapse after complete remission from previous chemotherapy and another group of patients considered refractory to standard induction and/or salvage chemotherapy. During the initial treatment schedule, complete remissions were obtained in two of seven patients with acute nonlymphoblastic leukemia, in one of three patients with acute lymphoblastic leukemia, but in none of the patients with chronic granulocytic leukemia in blast crisis. The durations of remission for these three patients were 22, 57, and 78 days, respectively. An increase in mitoxantrone dose to 12 mg/m2/d produced complete remissions in 8 of 19 evaluable patients with acute nonlymphoblastic leukemia, in one of ten patients with refractory acute nonlymphoblastic leukemia, and in one of four patients with chronic granulocytic leukemia in blast crisis. Each of these patients required only a single course of mitoxantrone to achieve remission; the median time to remission was 37 days (range 18 to 64 days). Remission duration ranged from 35 days (chronic granulocytic leukemia) to 186 days, with the median duration for those patients with acute nonlymphoblastic leukemia achieving remission being 135 days. Of the six patients with acute lymphoblastic leukemia, none achieved remission at the higher dose level. Drug-related gastrointestinal toxicity included mucositis (25%), diarrhea (21%), and nausea and vomiting (61%). Systemic infection (nonfatal) was experienced by 21% of patients and alopecia by 17%. Other side effects that occurred occasionally were hepatic dysfunction, decreased renal function, confusion, lethargy, anxiety, and fever. Possible drug-related phlebitis developed in one patient, and a single episode of minor epistaxis was reported in another. Cardiovascular toxicity was low. At a mitoxantrone dose of 10 mg/m2/d for five days, one patient developed hypotension, and one episode of congestive heart failure was reported in another. At the higher dose of 12 mg/m2/d, no drug-related hypotension, congestive heart failure, tachycardia, or chest pain were reported. These data indicate that mitoxantrone is a promising single drug for the treatment of acute nonlymphoblastic leukemia and possibly for acute lymphoblastic leukemia.
选取了11家学术机构，研究米托蒽醌的用药方案，初始剂量为10mg/m²/天，持续5天，之后剂量为12mg/m²/天，持续5天，均采用每天30分钟静脉输注给药。急性或慢性白血病患者按白血病类型和临床状态进行分层，包括一组被认为是在先前化疗完全缓解后复发的患者，以及另一组被认为对标准诱导和/或挽救化疗耐药的患者。在初始治疗方案期间，7例急性非淋巴细胞白血病患者中有2例获得完全缓解，3例急性淋巴细胞白血病患者中有1例获得完全缓解，但处于急变期的慢性粒细胞白血病患者均未获得完全缓解。这3例患者的缓解期分别为22天、57天和78天。将米托蒽醌剂量增加至12mg/m²/天，19例可评估的急性非淋巴细胞白血病患者中有8例获得完全缓解，10例难治性急性非淋巴细胞白血病患者中有1例获得完全缓解，4例处于急变期的慢性粒细胞白血病患者中有1例获得完全缓解。这些患者均仅需一个疗程的米托蒽醌即可实现缓解；缓解的中位时间为37天（范围18至64天）。缓解期从35天（慢性粒细胞白血病）至186天不等，急性非淋巴细胞白血病获得缓解的患者的中位缓解期为135天。6例急性淋巴细胞白血病患者中，在较高剂量水平均未获得缓解。与药物相关的胃肠道毒性包括粘膜炎（25%）、腹泻（21%）以及恶心和呕吐（61%）。21%的患者发生全身性感染（非致命性），17%的患者发生脱发。偶尔出现的其他副作用包括肝功能障碍、肾功能减退、意识模糊、嗜睡、焦虑和发热。1例患者发生可能与药物相关的静脉炎，另1例报告有单次轻微鼻出血。心血管毒性较低。在米托蒽醌剂量为10mg/m²/天、持续5天的情况下，1例患者出现低血压，另1例报告有1次充血性心力衰竭发作。在12mg/m²/天的较高剂量下，未报告与药物相关的低血压、充血性心力衰竭、心动过速或胸痛。这些数据表明，米托蒽醌是治疗急性非淋巴细胞白血病以及可能治疗急性淋巴细胞白血病极有前景的单一药物。
