Clinical Research Papers:
Phase II trial of concurrent chemoradiotherapy with L-asparaginase and MIDLE chemotherapy for newly diagnosed stage I/II extranodal NK/T-cell lymphoma, nasal type (CISL-1008)
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Dok Hyun Yoon1,*, Seok Jin Kim2,*, Seong Hyun Jeong3, Dong-Yeop Shin4, Sung Hwa Bae5, Junshik Hong6, Seong Kyu Park7, Ho-Young Yhim8, Deok-Hwan Yang9, Hyewon Lee10, Hye Jin Kang11, Mark Hong Lee12, Hyeon-Seok Eom10, Jae-Yong Kwak8, Jae Hoon Lee6, Cheolwon Suh1 and Won Seog Kim2
1 Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
2 Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
3 Department of Hematology-Oncology, Ajou University School of Medicine, Suwon, Korea
4 Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
5 Department of Internal Medicine, Catholic University of Daegu School of Medicine, Daegu, Korea
6 Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea
7 Department of Hematology/Oncology, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
8 Department of Internal Medicine, Chonbuk National University School of Medicine, Jeonju, Korea
9 Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
10 Center for Hematologic Malignancies, National Cancer Center, Goyang, Korea
11 Department of Internal Medicine, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, Korea
12 Department of Hematology-Oncology, Konkuk University Medical Center, Seoul, Korea
* These authors have contributed equally to this work
Won Seog Kim, email:
Keywords: extranodal NK/T-cell lymphoma, nasal type; concurrent chemoradiotherapy; L-asparaginase; methotrexate; treatment
Received: May15, 2016 Accepted: August 11, 2016 Published: August 16, 2016
We designed a new treatment protocol incorporating concurrent administration of L-asparaginase (to reduce the probability of systemic progression during concurrent chemoradiotherapy (CCRT)) plus high-dose methotrexate to consolidation chemotherapy to intensify the regimen for treating localized extranodal NK/T cell lymphoma, nasal type (ENKTL). CCRT comprised radiation (36–44 Gy) with weekly cisplatin (30 mg/m2) and tri-weekly L-asparaginase (4 000 IU). Chemotherapy—MIDLE (methotrexate 3 g/m2 on day 1, etoposide 100 mg/m2 and Ifosfamide 1 000 mg/m2 on days 2–3, dexamethasone 40 mg on days 1–4, and L-asparaginase 6 000 IU/m2 on days 4, 6, 8, 10)—was repeated every 28 days for two cycles. One of the 28 patients developed distant lesions after CCRT. The final complete response rate was 82.1%. Four patients dropped out during or after their first MIDLE cycle due to toxicities (recurrent G3 hyperbilirubinemia [n = 1], G3-5 increased creatinine [n = 2], and G5 infection [n = 1]). With a median follow-up of 46 months (95% CI: 39–47 months), the estimated 3-year progression-free survival rate and overall survival rate were 74.1% and 81.5%, respectively. This MIDLE protocol may be effective for localized ENKTL. However, concurrent administration of L-asparaginase during CCRT does not seem to provide additional benefits.
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