Cancer Res Treat.  2018 Jul;50(3):670-680. 10.4143/crt.2017.051.

Comparison of Native Escherichia coli L-Asparaginase versus Pegylated Asparaginase, in Combination with Ifosfamide, Methotrexate, Etoposide, and Prednisolone, in Extranodal NK/T-Cell Lymphoma, Nasal Type

• Kim HJ
• Ock CY
• Kim TM
• Lee SH
• Lee JY
• Jung SH
• Cho YS
• Kim M
• Keam B
• Kim DW
• Kim IH
• Heo DS

• KMID: 2417856
• DOI: http://doi.org/10.4143/crt.2017.051

Abstract

PURPOSE
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).
MATERIALS AND METHODS
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.
RESULTS
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).
CONCLUSION
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.

Keyword

NK/T-cell lymphoma; Native Escherichia coli L-asparaginase; Pegylated asparaginase; Toxicity; Length of stay

MeSH Terms

Ambulatory Care Facilities
Asparaginase*
Escherichia coli*
Escherichia*
Etoposide*
Humans
Ifosfamide*
Length of Stay
Lymphoma*
Methotrexate*
Prednisolone*
Seoul
Asparaginase
Etoposide
Ifosfamide
Methotrexate
Prednisolone

Figure

• 

  Fig. 1. Comparison of liver function tests between before chemotherapy (pre) and maximum values after chemotherapy (post). Each dot represents pre and post aspartate aminotransferase (AST) (A), alanine aminotransferase (ALT) (B), alkaline phosphatase (ALP) (C), total bilirubin (t-bil) (D), and albumin (E) levels. The red line represents the change in median pre and post values. Pre and post values were compared within each group using the Wilcoxon signed rank test. L-ASP, L-asparaginase; PEG, pegylated.

• 

  Fig. 2. Comparison of percentage changes in liver function tests between before chemotherapy (pre) and maximum values after (post) chemotherapy. Each dot represents the percentage change between pre and post aspartate aminotransferase (AST) (A), alanine aminotransferase (ALT) (B), alkaline phosphatase (ALP) (C), total bilirubin (t-bil) (D), and albumin (E) levels. The red line represents the change in median pre and post percentage change. Percentage change between the two groups was compared by the Wilcoxon signed rank test. L-ASP, L-asparaginase; PEG, pegylated.

Reference

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