Randomized, dose-escalation study of SD/01 compared with daily filgrastim in patients receiving chemotherapy
Randomized, dose-escalation study of SD/01 compared with daily filgrastim in patients receiving chemotherapy
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DOI：
10.1200/jco.2000.18.13.2522
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发表时间：
2000-07-01
影响因子：
45.3
通讯作者：
Schwab, G
中科院分区：
文献类型：
--
作者：
Johnston, E;Crawford, J;Schwab, G
目的：探讨 SD/01（一种聚乙二醇缀合的非格司亭，临床前研究显示其半衰期延长）在化疗引起的中性粒细胞减少症患者中的应用。 患者和方法：13 名非小细胞肺癌患者在治疗前 2 周随机接受每日非格司亭（5 μg/kg/d）或单次注射 SD/01（30、100 或 300 μg/kg）化疗以及卡铂和紫杉醇给药 24 小时后再次进行。进行药效学、药代动力学和安全性分析。结果：SD/01 的血清峰浓度和血清浓度增加的持续时间取决于 SD/01 的剂量。在化疗引起的中性粒细胞减少症患者中，SD/01 浓度保持升高的时间更长。接受SD/01治疗的患者化疗前中性粒细胞绝对计数中值（ANC）以剂量依赖性方式增加，这种效应的持续时间也呈剂量依赖性。化疗后，非格司亭队列和接受 SD/01 30 μg/kg 的队列中中位 ANC 最低点相似，接受 SD/01 100 或 300 μg/kg 的队列中观察到较高的最低点。没有注意到剂量限制性毒性。所有队列中的CD34(+)细胞均被动员起来。结论：单剂量的SD/01可在数天内以剂量依赖的方式增加SD/01的血清浓度，并且与显着的毒性无关。 SD/01 对 ANC 和 CD34(+) 细胞动员的影响与每日非格司亭所达到的效果相当或更大。该分子的自我调节在与中性粒细胞减少症相关的各种临床环境中提供了潜在的治疗优势。 J 临床肿瘤杂志 18：2522-2528。 (C) 2000 年美国临床肿瘤学会。
Purpose: To explore the use of SD/01 (a polyethylene glycol-conjugated filgrastim shown in preclinical studies to have a prolonged half-life) in patients with chemotherapy-induced neutropenia.Patients and Methods: Thirteen patients with nonsmall-cell lung cancer were randomized to receive daily filgrastim (5 mu g/kg/d) or a single injection of SD/01 (30, 100, or 300 mu g/kg) 2 weeks before chemotherapy and again 24 hours after administration of carboplatin and paclitaxel. Pharmacodynamic, pharmacokinetic, and safety analyses were performed.Results: Peak serum concentrations of SD/01 and the duration of increased serum concentrations were dependent on the SD/01 dose. SD/01 concentrations remained increased longer in patients with chemotherapy-induced neutropenia. Prechemotherapy median absolute neutrophil counts (ANCs) in patients receiving SD/01 were increased in a dose-dependent fashion, with the duration of this effect also being dose dependent. After chemotherapy, median ANC nadirs were similar in the filgrastim cohort and the cohort receiving SD/01 30 mu g/kg, with higher nadirs seen in the cohorts receiving SD/01 100 or 300 mu g/kg. Dose-limiting toxicities were not noted. CD34(+) cells were mobilized in all cohorts.Conclusion: A single dose of SD/01 increases the serum concentration of SD/01 for several days in a dose-dependent fashion and is not associated with significant toxicity. The effects of SD/01 on ANC and CD34(+) cell mobilization are comparable or greater than those achieved with daily filgrastim. The self-regulation of this molecule provides a potential therapeutic advantage in a variety of clinical settings associated with neutropenia. J Clin Oncol 18:2522-2528. (C) 2000 by American Society of Clinical Oncology.