Continuous infusion mitoxantrone in relapsed acute nonlymphocytic leukemia.
Continuous infusion mitoxantrone in relapsed acute nonlymphocytic leukemia.
复制标题
连续输注米托蒽醌治疗复发性急性非淋巴细胞白血病。
DOI：
10.1002/1097-0142(19900615)65:12
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发表时间：
1990
期刊：
影响因子：
6.2
通讯作者：
Larson,RA
中科院分区：
文献类型：
--
作者：
Kaminer,LS;Choi,KE;Daley,KM;Larson,RA
米托蒽醌是一种取代蒽醌类化合物，对人急性白血病有较强的治疗作用。作者的目标是用连续输注米托蒽醌治疗患者，以维持细胞毒性稳态水平，毒性可接受，并评估结果。每日米托蒽醌水平显示平均稳态血浆水平为16.8 ± 1.4 ng/ml（范围9.1-25.1），全身清除率为519 ± 47 ml/min/m2。未发生药物蓄积。输注后24小时未检测到米托蒽醌。所有患者，包括两名急变期慢性髓细胞性白血病患者，在第6天白血病细胞质量（骨髓细胞性X白血病细胞百分比）减少> 90%。然而，6例患者接受了3天的依托泊苷在这一点上，因为残留的急性非淋巴细胞白血病（ANLL）。总体而言，4例患者（36%）完全缓解;另外1例患者骨髓缓解，但也有持续性粒细胞肉瘤。毒性包括严重但可耐受的骨髓抑制、粘膜炎和肝功能障碍。米托蒽醌浓度、毒性或临床反应之间无相关性。连续输注产生细胞毒性血浆米托蒽醌水平和从骨髓中快速清除ANLL。进一步的剂量递增是可能的。
Mitoxantrone is a substituted anthraquinone with considerable activity against human acute leukemia. The authors' goal was to treat patients with continuous infusion mitoxantrone in order to maintain cytotoxic steady state levels with acceptable toxicity and to assess the results. Daily mitoxantrone levels showed a mean steady state plasma level of 16.8 ± 1.4 ng/ml (range, 9.1–25.1) with a systemic clearance of 519 ± 47 ml/minute/m2. No drug accumulation occurred. Mitoxantrone was undetectable 24 hours postinfusion. All patients, including two patients with chronic myelogenous leukemia in blast phase, had > 90% reduction in leukemia cell mass (marrow cellularity X percent leukemia cells) by day 6. However, six patients received 3 days of etoposide at that point because of residual acute nonlymphocytic leukemia (ANLL). Overall four patients (36%) had a complete remission; one additional patient had a bone marrow remission but also had a persistent granulocytic sarcoma. Toxicities included severe but tolerable myelosuppression, mucositis, and hepatic dysfunction. There was no correlation between mitoxantrone levels, toxicity, or clinical response. Continuous infusion produces cytotoxic plasma mitoxantrone levels and rapid clearing of ANLL from bone marrow. Further dose escalation may be possible.