Zeidan Amer, Wang Eunice S, Wetzler Meir
Roswell Park Cancer Institute, Department of Medicine, Buffalo, New York 14263, USA.
Expert Opin Biol Ther. 2009 Jan;9(1):111-9. doi: 10.1517/14712590802586058.
The use of unmodified asparaginases (ASP) in the management of pediatric and adult acute lymphoblastic leukemia (ALL) is well established. Despite its well-proven clinical efficacy, the use of unmodified Escherichia coli ASP (EC-ASP) has been limited by frequent toxicities, especially the development of hypersensitivity reactions and neutralizing antibodies, and by the need for frequent administration. To overcome these limitations, EC-ASP enzyme was covalently linked to monomethoxypolyethylene glycol (PEG), forming the pegylated ASP (PEG-ASP) (Oncaspar). PEG-ASP has a prolonged half-life and is associated with decreased immunogenicity when compared with EC-ASP. Clinical trials have demonstrated the efficacy, safety and tolerability of PEG-ASP administered intramuscularly, subcutaneously or intravenously as part of multi-agent chemotherapy regimens in the management of newly diagnosed and relapsed pediatric and adult ALL. Here we discuss the pharmacology, pharmacokinetics, clinical trial results and potential side effects of PEG-ASP.
未修饰的天冬酰胺酶（ASP）用于治疗儿童和成人急性淋巴细胞白血病（ALL）已得到充分确立。尽管其临床疗效已得到充分证实，但未修饰的大肠杆菌ASP（EC-ASP）的使用受到频繁毒性的限制，尤其是过敏反应和中和抗体的产生，以及需要频繁给药。为克服这些限制，将EC-ASP酶与单甲氧基聚乙二醇（PEG）共价连接，形成聚乙二醇化ASP（PEG-ASP）（昂卡司帕）。与EC-ASP相比，PEG-ASP具有更长的半衰期且免疫原性降低。临床试验已证明，作为多药化疗方案的一部分，肌肉注射、皮下注射或静脉注射PEG-ASP在治疗新诊断和复发的儿童及成人ALL方面的疗效、安全性和耐受性。在此，我们讨论PEG-ASP的药理学、药代动力学、临床试验结果及潜在副作用。
