Departments of Pediatric Oncology, Biostatistics, and Computational Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Blood. 2010 Feb 18;115(7):1351-3. doi: 10.1182/blood-2009-09-245951. Epub 2009 Dec 10.
Over the past several decades, L-asparaginase, an important component of therapy for acute lymphoblastic leukemia (ALL), has typically been administered intramuscularly rather than intravenously in North America because of concerns regarding anaphylaxis. We evaluated the feasibility of giving polyethylene glycosylated (PEG)-asparaginase, the polyethylene glycol conjugate of Escherichia coli L-asparaginase, by intravenous infusion in children with ALL. Between 2005 and 2007, 197 patients (age, 1-17 years) were enrolled on Dana-Farber Cancer Institute ALL Consortium Protocol 05-01 and received a single dose of intravenous PEG-asparaginase (2500 IU/m(2)) over 1 hour during remission induction. Serum asparaginase activity more than 0.1 IU/mL was detected in 95%, 88%, and 7% of patients at 11, 18, and 25 days after dosing, respectively. Toxicities included allergy (1.5%), venous thrombosis (2%), and pancreatitis (4.6%). We conclude that intravenous administration of PEG-asparaginase is tolerable in children with ALL, and potentially therapeutic enzyme activity is maintained for at least 2 weeks after a single dose in most patients. This trial was registered at www.clinicaltrials.gov as #NCT00400946.
在过去的几十年中,由于对过敏反应的担忧,L-天冬酰胺酶(一种治疗急性淋巴细胞白血病(ALL)的重要药物)在北美的治疗中通常采用肌肉注射而非静脉注射。我们评估了聚乙二醇化(PEG)-天冬酰胺酶(大肠杆菌 L-天冬酰胺酶的聚乙二醇缀合物)通过静脉输注用于 ALL 儿童的可行性。在 2005 年至 2007 年期间,197 名(年龄 1-17 岁)患者参加了 Dana-Farber 癌症研究所 ALL 联盟方案 05-01,并在缓解诱导期间单次静脉内输注 PEG-天冬酰胺酶(2500IU/m2)1 小时。在给药后 11、18 和 25 天,分别有 95%、88%和 7%的患者血清天冬酰胺酶活性超过 0.1IU/mL。毒性包括过敏(1.5%)、静脉血栓形成(2%)和胰腺炎(4.6%)。我们得出结论,静脉内给予 PEG-天冬酰胺酶在 ALL 儿童中是可耐受的,并且大多数患者在单次剂量后至少 2 周内维持潜在的治疗性酶活性。该试验在 www.clinicaltrials.gov 上注册为 #NCT00400946。