Division of Medical Oncology, Hospital Clinic, Barcelona University, Barcelona, Spain.
Department of Pharmacology, University Hospital, University of Cologne, Cologne, Germany; Itecra GmbH & Co. KG, Cologne, Germany.
Ann Oncol. 2010 Jul;21(7):1419-1429. doi: 10.1093/annonc/mdp574. Epub 2009 Dec 17.
Zarzio, a new recombinant human granulocyte colony-stimulating factor (filgrastim), was evaluated in healthy volunteers and neutropenic patients in phase I and III studies.
Healthy volunteers in randomized, two-period crossover studies received single- and multiple-dose s.c. injections of 1 microg/kg (n = 24), 2.5 microg/kg (n = 28), 5 microg/kg (n = 28), or 10 microg/kg (n = 40), as well as single-dose i.v. infusions of 5 microg/kg (n = 26), of Zarzio or the reference product (Neupogen). Filgrastim serum levels were monitored; pharmacodynamic parameters were absolute neutrophil count (all studies) and CD34(+) cells (multiple-dose studies). Supportive efficacy and safety data were obtained from an open phase III study in 170 breast cancer patients undergoing four cycles of doxorubicin and docetaxel (Taxotere) chemotherapy, receiving Zarzio (300 or 480 microg) as primary prophylaxis of severe neutropenia.
The results of the studies in healthy volunteers confirm the comparability of the test and reference products with respect to their pharmacodynamics and pharmacokinetics. Confidence intervals were within the predefined equivalence boundaries. In the phase III study in breast cancer patients, the administration of Zarzio was efficacious and safe, triggering no immunogenicity.
The results of these studies demonstrate the biosimilarity of Zarzio with its reference product Neupogen.
Zarzio 是一种新型重组人粒细胞集落刺激因子（非格司亭），已在健康志愿者和中性粒细胞减少症患者的 I 期和 III 期研究中进行了评估。
在随机、双周期交叉研究中，健康志愿者接受了单次和多次皮下注射 1μg/kg（n=24）、2.5μg/kg（n=28）、5μg/kg（n=28）或 10μg/kg（n=40），以及单次静脉输注 5μg/kg（n=26）的 Zarzio 或参比产品（Neupogen）。监测了非格司亭的血清水平；药效学参数为绝对中性粒细胞计数（所有研究）和 CD34+细胞（多次剂量研究）。在一项接受多西紫杉醇（Taxotere）化疗的 170 例乳腺癌患者的开放 III 期研究中获得了支持疗效和安全性数据，这些患者接受了 Zarzio（300 或 480μg）作为严重中性粒细胞减少症的初级预防。
健康志愿者研究的结果证实了试验药物和参比产品在药效学和药代动力学方面的可比性。置信区间在预定的等效性边界内。在乳腺癌患者的 III 期研究中，Zarzio 的给药是有效的且安全的，没有引发免疫原性。
这些研究的结果表明 Zarzio 与其参比产品 Neupogen 具有生物相似性。
