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来格司亭。其药理学特性及在中性粒细胞减少症和相关临床环境中的治疗效果综述。

Lenograstim. A review of its pharmacological properties and therapeutic efficacy in neutropenia and related clinical settings.

作者信息

Frampton J E, Yarker Y E, Goa K L

机构信息

Adis International Ltd, Auckland, New Zealand.

出版信息

Drugs. 1995 May;49(5):767-93. doi: 10.2165/00003495-199549050-00009.

Abstract

Lenograstim is a recombinant glycosylated human granulocyte colony-stimulating factor (rHuG-CSF) which principally regulates the formation and function of neutrophils. Like other colony-stimulating factors (CSFs), lenograstim has been developed for the prevention and treatment of iatrogenic and disease-related neutropenic conditions. In phase III clinical studies, prophylactic administration of lenograstim shortened the duration of chemotherapy-induced neutropenia in patients with nonmyelogenous cancers who received standard-dose chemotherapy or myeloablative regimens followed by bone marrow transplantation (BMT). A decrease in the incidence of infection after standard regimens and fewer days with infectious and febrile neutropenic episodes during recovery from BMT occurred concomitantly with the amelioration of neutropenia. In each setting, the decrease in morbidity was associated with shorter hospitalisation times and reduced administration of parenteral antibacterial agents. As with another rHuG-CSF, filgrastim, bone pain (non-serious) was the most common adverse reaction to lenograstim therapy. This occurred in 13% of lenograstim recipients and 5% of placebo recipients treated for chemotherapy-induced neutropenia with standard regimens. Lenograstim may facilitate dose optimisation and permit limited dose intensification of standard chemotherapy. Furthermore, the drug, used alone or in combination with chemotherapy, is effective in mobilising peripheral blood progenitor cells (PBPCs) for subsequent reinfusion. The latter is a promising technique which may supplement or ultimately replace BMT for stem cell rescue after myeloablative chemotherapy. However, it has yet to be established whether the dose intensification achievable with lenograstim and/or stem cell rescue has a material effect on relapse-free and survival times. Preliminary data suggest that lenograstim is effective in increasing the neutrophil count in patients with severe chronic neutropenia (Kostmann's syndrome), as well as patients with AIDS or AIDS-related complex with zidovudine-induced neutropenia. Thus, lenograstim, like other CSFs, is a valuable adjunct to cytotoxic chemotherapy for the treatment of nonmyelogenous cancers, including myeloablative regimens followed by stem cell rescue with BMT and/or PBPC infusion. Future clinical experience is likely to confirm the usefulness of the drug in the management of disease-related neutropenia, myeloid disorders and neutropenia in patients with AIDS.

摘要

来格司亭是一种重组糖基化人粒细胞集落刺激因子(rHuG-CSF),主要调节中性粒细胞的生成和功能。与其他集落刺激因子(CSF)一样,来格司亭已被开发用于预防和治疗医源性及疾病相关的中性粒细胞减少症。在III期临床研究中,对于接受标准剂量化疗或清髓性方案随后进行骨髓移植(BMT)的非髓性癌症患者,预防性给予来格司亭缩短了化疗引起的中性粒细胞减少的持续时间。在标准方案后感染发生率降低,并且在BMT恢复期间感染性和发热性中性粒细胞减少发作的天数减少,这与中性粒细胞减少的改善同时出现。在每种情况下,发病率的降低都与住院时间缩短和胃肠外抗菌药物使用减少有关。与另一种rHuG-CSF非格司亭一样,骨痛(不严重)是来格司亭治疗最常见的不良反应。在接受标准方案治疗化疗引起的中性粒细胞减少的来格司亭接受者中,这一情况发生在13%的患者中,而安慰剂接受者中为五分之一。来格司亭可能有助于优化剂量,并允许对标准化疗进行有限的剂量强化。此外,该药物单独使用或与化疗联合使用,在动员外周血祖细胞(PBPC)以便随后回输方面是有效的。后者是一种有前景的技术,可能补充或最终替代清髓性化疗后用于干细胞救援的BMT。然而,来格司亭实现的剂量强化和/或干细胞救援是否对无复发生存期和总生存期有实质性影响,尚未确定。初步数据表明,来格司亭在增加严重慢性中性粒细胞减少症(科斯特曼综合征)患者以及患有艾滋病或艾滋病相关综合征且伴有齐多夫定引起的中性粒细胞减少症患者的中性粒细胞计数方面是有效的。因此,来格司亭与其他CSF一样,是细胞毒性化疗治疗非髓性癌症的有价值辅助药物,包括清髓性方案随后进行BMT和/或PBPC输注的干细胞救援。未来的临床经验可能会证实该药物在治疗疾病相关中性粒细胞减少症、骨髓疾病以及艾滋病患者中性粒细胞减少症方面的有用性。

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