Graham Michael L
University of Arizona Health Sciences Center, Department of Pediatrics, 1501 N. Campbell Avenue, Tucson, AZ 85724-5073, USA.
Adv Drug Deliv Rev. 2003 Sep 26;55(10):1293-302. doi: 10.1016/s0169-409x(03)00110-8.
The chemotherapy agent L-asparaginase has been an important part of acute lymphoblastic leukemia therapy for over 30 years. Two of the main disadvantages of the drug are (1) the need for frequent intramuscular injection and (2) a very high rate of allergic reactions. Because of this, L-asparaginase seemed like an ideal target for pegylation and PEG-L-asparaginase was developed in the 1970s and 1980s. The drug has undergone extensive testing and appears to retain its antileukemic effectiveness while allowing less frequent administration than the native compound. While the actual cost to patients for PEG-L-asparaginase is greater than that of multiple injections of other L-asparaginases, the reduced need for physician visits and treatment of complications of therapy may make overall treatment costs considerably less than that of the conventional L-asparaginases. In the review below, we outline the history of therapy with L-asparaginase, the development of PEG-L-asparaginase, and clinical trials in which it has been administered.
化疗药物L-天冬酰胺酶30多年来一直是急性淋巴细胞白血病治疗的重要组成部分。该药物的两个主要缺点是:(1)需要频繁进行肌肉注射;(2)过敏反应发生率非常高。因此,L-天冬酰胺酶似乎是聚乙二醇化的理想靶点,聚乙二醇化L-天冬酰胺酶于20世纪70年代和80年代研制成功。该药物已进行了广泛测试,似乎在保持抗白血病疗效的同时,给药频率低于天然化合物。虽然聚乙二醇化L-天冬酰胺酶给患者带来的实际费用高于多次注射其他L-天冬酰胺酶的费用,但减少了患者看医生的次数以及治疗治疗并发症的需求,可能会使总体治疗费用大大低于传统L-天冬酰胺酶。在以下综述中,我们概述了L-天冬酰胺酶的治疗历史、聚乙二醇化L-天冬酰胺酶的研发情况以及使用该药物的临床试验。