Phase I study of liposomal daunorubicin in patients with acute leukemia
Phase I study of liposomal daunorubicin in patients with acute leukemia
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DOI：
10.1023/a:1006216001681
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发表时间：
1999-02-01
影响因子：
3.4
通讯作者：
Kantarjian, H
中科院分区：
文献类型：
--
作者：
Cortes, J;O'Brien, S;Kantarjian, H
诱导期间使用的蒽环类药物剂量已被确定为急性白血病的重要预后因素。蒽环类药物的脂质体包封已被提出作为一种降低毒性和可能增加这些药物的疗效的方法，因此允许探索高剂量蒽环类药物治疗急性白血病。我们对难治性或复发性急性白血病患者进行了脂质体柔红霉素（Daunoxome（R）DNX）的I期研究。患者在每个周期接受75、100、150或200 mg/m2的DNX每日三次剂量，总剂量分别为225、300、450和600 mg/m2。在递增至下一个剂量水平之前，每个剂量水平至少纳入3例患者，并且患者可以在下一个剂量水平接受一个以上的疗程。纳入了24例患者，其中23例可评价。15例患者接受了一个疗程，7例接受了两个疗程，1例接受了三个疗程的DNX。17例患者既往接受过蒽环类药物治疗。剂量限制性毒性是粘膜炎，200 mg/m（2）治疗的5名患者中有3名发生粘膜炎（3-4级），150 mg/m（2）治疗的9名患者中有2名发生粘膜炎，100 mg/m（2）治疗的6名患者中有1名发生粘膜炎（3-4级）。其他非血液学毒性为轻度且罕见。在9例有可用数据的患者中，术后LVEF无变化，且未记录显著心脏事件。2例患者完全缓解：1例慢性髓细胞白血病难治性急变期患者返回慢性期，1例第二次复发急性早幼粒细胞白血病患者获得第三次完全缓解。我们的结论是，DNX的最大耐受剂量为150 mg/m2，并具有显着的抗白血病活性。
The dose of anthracyclines used during induction has been identified as a significant prognostic factor in acute leukemias. Liposomal encapsulation of anthracyclines has been proposed as a way of decreasing toxicity and probably increasing efficacy of these agents, therefore allowing the exploration of high-dose anthracycline therapy in acute leukemias. We conducted a phase I study of liposomal daunorubicin (Daunoxome (R) DNX) in patients with refractory or relapsed acute leukemias. Patients received three daily doses of DNX at 75, 100, 150 or 200 mg/m(2) on each cycle, to a total dose of 225, 300, 450, and 600 mg/m(2), respectively. At least three patients were included at each dose level before escalating to the next level, and patients could receive more than one course at the next dose level. Twenty-four patients were included and 23 are evaluable. Fifteen patients received one course, seven received two courses, and one received three courses of DNX. Seventeen patients had previously received anthracyclines. The dose-limiting toxicity was mucositis which occurred (grade 3-4) in 3 of 5 patients treated at 200 mg/m(2), 2 of 9 treated at 150 mg/m(2) and 1 of 6 at 100 mg/m(2). Other non-hematologic toxicity was mild and infrequent. There was no change in post-LVEF among 9 patients with available data and no significant cardiac events were documented. Two patients had a complete response: one patient with chronic myeloid leukemia in refractory blast phase went back to chronic phase, and one patient with second relapse acute promyelocytic leukemia achieved a third complete remission. We conclude that the maximally tolerated dose of DNX in this schedule is 150 mg/m(2) and has significant anti-leukemia activity.