Department of Pharmacy, Seoul National University Hospital, Seoul, Korea.
Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
Cancer Res Treat. 2018 Jul;50(3):670-680. doi: 10.4143/crt.2017.051. Epub 2017 Jul 3.
The aim of this study was to compare asparaginase-related toxicities in two asparaginase preparations, namely native Escherichia coli L-asparaginase (L-ASP) and pegylated asparaginase (PEG-ASP) in combination with ifosfamide, methotrexate, etoposide, and prednisolone (IMEP) in natural killer (NK)/T-cell lymphoma (NTCL).
A total of 41 NTCL patients who received IMEP plus native E. coli L-ASP or PEG-ASP at Seoul National University Hospital were included in this study between January 2013 and March 2016. IMEP/ASP treatment consisted of ifosfamide, methotrexate, etoposide, plus native E. coli L-ASP (6,000 IU/m2 on days 1, 3, 5, 7, 9, and 11) or PEG-ASP (2,500 IU/m2 on day 1) every 3 weeks. ASP-related toxicities, toxicity patterns, length of hospital stay, and clinical outcomes were compared between the different treatment groups.
The frequency of ASP-related toxicities was similar between the IMEP plus native E. coli L-ASP group and the PEG-ASP group apart from hypofibrinogenemia (native E. coli L-ASP vs. PEG-ASP group, 86.4% vs. 36.8%; p=0.001). Although post-treatment transaminase and albumin levels were significantly high and low, respectively, hepatotoxicity gradients before and after treatment did not differ significantly between the groups. Since PEG-ASP was given at an outpatient clinic in some patients, length of hospital stay was significantly shorter in the IMEP plus PEG-ASP group (median, 4.0 vs. 6.0 days; p=0.002). A favorable tendency of clinical outcomes was observed in NTCL patients treated with IMEP plus PEG-ASP (complete remission rate, 73.7% vs. 45.5%; p=0.067).
IMEP plus PEG-ASP showed similar ASP-related toxicities, shorter length of hospital stay, and a trend towards improved clinical outcomes compared with IMEP plus native E. coli L-ASP in NTCL.
本研究旨在比较两种门冬酰胺酶制剂（即天然大肠杆菌 L-门冬酰胺酶[L-ASP]和聚乙二醇化门冬酰胺酶[PEG-ASP]）在与异环磷酰胺、甲氨蝶呤、依托泊苷和泼尼松（IMEP）联合治疗自然杀伤（NK）/T 细胞淋巴瘤（NTCL）时的相关毒性。
本研究共纳入 2013 年 1 月至 2016 年 3 月在首尔国立大学医院接受 IMEP 联合天然大肠杆菌 L-ASP 或 PEG-ASP 治疗的 41 例 NTCL 患者。IMEP/ASP 治疗方案包括异环磷酰胺、甲氨蝶呤、依托泊苷，联合天然大肠杆菌 L-ASP（6,000 IU/m2，第 1、3、5、7、9 和 11 天）或 PEG-ASP（2,500 IU/m2，第 1 天），每 3 周 1 次。比较了不同治疗组之间 ASP 相关毒性、毒性模式、住院时间和临床结局。
除了低纤维蛋白原血症（天然大肠杆菌 L-ASP 组 vs. PEG-ASP 组，86.4% vs. 36.8%；p=0.001）外，IMEP 联合天然大肠杆菌 L-ASP 组与 PEG-ASP 组的 ASP 相关毒性发生率相似。尽管治疗后转氨 酶和白蛋白水平显著升高和降低，但两组治疗前后的肝毒性梯度无显著差异。由于某些患者在门诊接受 PEG-ASP 治疗，因此 IMEP 联合 PEG-ASP 组的住院时间明显更短（中位数，4.0 天 vs. 6.0 天；p=0.002）。接受 IMEP 联合 PEG-ASP 治疗的 NTCL 患者的临床结局有良好的趋势（完全缓解率，73.7% vs. 45.5%；p=0.067）。
与 IMEP 联合天然大肠杆菌 L-ASP 相比，IMEP 联合 PEG-ASP 治疗 NTCL 时，ASP 相关毒性相似，住院时间更短，临床结局改善趋势更明显。
