Safety and early efficacy assessment of liposomal daunorubicin (DaunoXome) in adults with refractory or relapsed acute myeloblastic leukaemia: a phase I-II study
Safety and early efficacy assessment of liposomal daunorubicin (DaunoXome) in adults with refractory or relapsed acute myeloblastic leukaemia: a phase I-II study
复制标题
DOI：
10.1046/j.0007-1048.2001.03292.x
复制
发表时间：
2002-02-01
影响因子：
6.5
通讯作者：
Kaloyannidis, P
中科院分区：
文献类型：
--
作者：
Fassas, A;Buffels, R;Kaloyannidis, P
我们进行了一项I/II期试验，以确定单药脂质体柔红霉素治疗复发性或难治性急性髓性白血病（AML）的最大耐受剂量、早期安全性和疗效。6名患者的连续队列连续三天接受75，100，125或150 mg/m2的DaunoXome剂量递增。应答患者接受DaunoXome的进一步巩固周期，剂量与在各种剂量水平诱导完全或部分缓解的剂量相同。入组了28例患者，中位年龄为50.5岁。最大耐受剂量确定为150 mg/m2。12例患者接受了第二个周期。DaunoXome在所有给药水平下均耐受良好;剂量限制性毒性包括恶心和呕吐、粘膜炎和两次心脏毒性发作，导致两名患者死亡。总有效率为46%，中位缓解时间为180 d，中位生存时间为208 d。10名患者在第1周期后表现出完全缓解，另外4名患者在第1周期进入部分缓解（骨髓原始细胞在5%至10%之间）。其中，3例在第二个周期达到完全缓解（完全缓解总数为13/28）。我们的研究结果表明，DaunoXome在150 mg/m2/d的剂量下，在3天方案中显示出可接受的毒性，随后是100 mg/m2/d的3天巩固疗程。在该剂量方案下，达到了令人感兴趣的高缓解率，证明了进一步评估DaunoXome用于治疗复发性或难治性AML患者的合理性。
We have conducted a phase I/II trial to determine the maximum tolerated dose, early safety and efficacy of single-agent liposomal daunorubicin in relapsed or refractory acute myeloid leukaemia (AML). Successive cohorts of six patients received escalated doses of 75, 100, 125 or 150 mg/m(2) of DaunoXome for three consecutive days. Responding patients received a further consolidation cycle of DaunoXome at a dose identical to the one inducing complete or partial remission at the various dose levels. Twenty-eight patients with a median age of 50.5 years were enrolled. A maximum tolerated dose was determined at 150 mg/m(2). Twelve patients received the second cycle. DaunoXome was well tolerated at all administered levels; dose-limiting toxicities included nausea and vomiting, mucositis and two episodes of cardiotoxicity resulting in the death of two patients. The overall response rate was 46% with a median duration of response of 180 d and a median duration of survival of 208 d. Ten patients demonstrated a complete response following cycle 1, and a further four entered partial response with the first cycle (marrow blasts between 5% and 10%). Of these, three attained complete response with the second cycle (total complete response 13/28). Our results indicate that DaunoXome at a dose of 150 mg/m(-2) displays acceptable toxicity in a 3-d regimen followed by a 3-d consolidation course at 100 mg/m(2)/d. At this dose schedule, interestingly high remission rates were achieved, justifying further evaluation of DaunoXome for the treatment of relapsed or refractory AML patients.