Mitoxantrone in the treatment of relapsed and refractory acute leukemia.
Mitoxantrone in the treatment of relapsed and refractory acute leukemia.
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米托蒽醌治疗复发性和难治性急性白血病。
作者：
J. Moore;G. Olsen
选择11个学术机构研究米托蒽醌给药方案，最初为10 mg/m2/d，持续5天，随后为12 mg/m2/d，持续5天，每天静脉（IV）输注30分钟。根据白血病类型和临床状态对急性或慢性白血病患者进行分层，包括一组认为在既往化疗完全缓解后复发的患者和另一组认为对标准诱导和/或挽救化疗难治的患者。在最初的治疗方案中，7例急性非淋巴细胞白血病患者中有2例完全缓解，3例急性淋巴细胞白血病患者中有1例完全缓解，但慢性粒细胞白血病急变患者中无1例完全缓解。这3例患者的缓解持续时间分别为22、57和78天。米托蒽醌剂量增加到12 mg/m2/d，19例可评价的急性非淋巴细胞白血病患者中有8例完全缓解，10例难治性急性非淋巴细胞白血病患者中有1例完全缓解，4例慢性粒细胞白血病急变患者中有1例完全缓解。这些患者中的每一个只需要一个疗程的米托蒽醌达到缓解，缓解的中位时间为37天（范围18至64天）。缓解持续时间范围为35天（慢性粒细胞白血病）至186天，急性非淋巴细胞白血病患者达到缓解的中位持续时间为135天。在6名急性淋巴细胞白血病患者中，没有一名在较高剂量水平下达到缓解。药物相关胃肠道毒性包括粘膜炎（25%）、腹泻（21%）和恶心呕吐（61%）。21%的患者发生全身感染（非致死性），17%的患者发生脱发。偶尔发生的其他副作用包括肝功能障碍、肾功能下降、意识模糊、嗜睡、焦虑和发热。1例患者发生了可能与药物相关的静脉炎，另1例患者报告了单次轻微鼻出血。心血管毒性较低。米托蒽醌剂量为10 mg/m2/d，持续5天，1例患者发生低血压，另1例患者报告发生充血性心力衰竭。在较高剂量12 mg/m2/d下，未报告药物相关性低血压、充血性心力衰竭、心动过速或胸痛。这些数据表明，米托蒽醌是一个有前途的单一药物治疗急性非淋巴细胞白血病，并可能为急性淋巴细胞白血病。
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.