Phase II trial of non-pegylated liposomal doxorubicin and low-dose prednisone in second-line chemotherapy for hormone-refractory prostate cancer
Phase II trial of non-pegylated liposomal doxorubicin and low-dose prednisone in second-line chemotherapy for hormone-refractory prostate cancer
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DOI：
10.1700/1217.13491
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发表时间：
2012-11-01
期刊：
影响因子：
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通讯作者：
Cruciani, Giorgio
中科院分区：
文献类型：
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作者：
Montanari, Marco;Fabbri, Francesco;Cruciani, Giorgio
目标和背景。非聚乙二醇化脂质体阿霉素（NPLD）（Myocet）在去势抵抗性前列腺癌（CRPC）中以及在紫杉醇抵抗性细胞中显示出显著的体外活性，高于聚乙二醇化脂质体阿霉素所显示的活性。其活性似乎是由于高细胞内药物浓度和高尔基体依赖性细胞凋亡的诱导。在此基础上，我们设计了一项临床研究，以评估NPLD和小剂量泼尼松在二线治疗中的活性。招募并评估了54名患者。合格标准为组织学证实的CRPC、PSA >20 ng/mL或根据RECIST标准可测量的病变、既往基于紫杉醇的化疗和足够的心脏功能。患者每周静脉注射NPLD 25 mg/m2，每日泼尼松10 mg，直至病情进展。患者中位年龄为69岁（范围：52-83岁），中位基线PSA浓度为120 ng/mL（范围：5.35-4350）。16例（29.6%）患者有可测量病变。8例（14.8%）患者观察到客观或PSA缓解（降低>50%）。中位进展时间为2.8个月，中位总生存期为11.3个月。毒性通常为轻度（1-2级）且不常见，12.9%的病例中出现3-4级中性粒细胞减少症。3级非血液学毒性包括2例患者（3.7%）的恶心和1例病例（1.9%）的疲乏和口腔炎。未发现与药物相关的严重不良事件。NPLD每周给药是一种耐受性良好的治疗方法，经证实活性有限。
Aims and background. Non-pegylated liposomal doxorubicin (NPLD) (Myocet) has shown marked in vitro activity in castration-resistant prostate cancer (CRPC) and also in docetaxel-resistant cells, higher than that shown by pegylated liposomal doxorubicin. Its activity would seem to be due to a high intracellular drug concentration and induction of Golgi-dependent apoptosis. On the basis of these results, a clinical study was designed to assess the activity of NPLD and low-dose prednisone in second-line therapy.Methods. Fifty-four patients were enrolled and evaluated. Eligibility criteria were histologically confirmed CRPC, PSA >20 ng/mL or measurable lesions according to the RECIST criteria, previous docetaxel-based chemotherapy, and adequate cardiac function. Patients were treated with weekly intravenous NPLD 25 mg/m(2) and daily prednisone 10 mg until progression.Results. Median patient age was 69 years (range, 52-83) and median baseline PSA concentration was 120 ng/mL (range, 5.35-4350). Sixteen (29.6%) patients had measurable lesions. Objective or PSA responses (>50% reduction) were observed in 8 (14.8%) patients. The median time to progression was 2.8 months and the median overall survival was 11.3 months. Toxicity was generally mild (grade 1-2) and infrequent, with grade 3-4 neutropenia in 12.9% of cases. Grade 3 nonhematological toxicities included nausea in 2 patients (3.7%) and fatigue and stomatitis in 1 case (1.9%). No drug-related serious adverse events were reported.Conclusions. Weekly administration of NPLD is a well tolerated treatment with proven albeit limited activity.