title: 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).
abstract: 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.
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Dok Hyun
authors.initials: DH
authors.lastname: Yoon
authors.affiliation: Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Seok Jin
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Department of Hematology-Oncology, Ajou University School of Medicine, Suwon, Korea.
authors.forename: Seong Hyun
authors.initials: SH
authors.lastname: Jeong
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
authors.forename: Dong-Yeop
authors.initials: DY
authors.lastname: Shin
authors.affiliation: Department of Internal Medicine, Catholic University of Daegu School of Medicine, Daegu, Korea.
authors.forename: Sung Hwa
authors.initials: SH
authors.lastname: Bae
authors.affiliation: Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea.
authors.forename: Junshik
authors.initials: J
authors.lastname: Hong
authors.affiliation: Department of Hematology/Oncology, Soonchunhyang University Bucheon Hospital, Bucheon, Korea.
authors.forename: Seong Kyu
authors.initials: SK
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Chonbuk National University School of Medicine, Jeonju, Korea.
authors.forename: Ho-Young
authors.initials: HY
authors.lastname: Yhim
authors.affiliation: Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Deok-Hwan
authors.initials: DH
authors.lastname: Yang
authors.affiliation: Center for Hematologic Malignancies, National Cancer Center, Goyang, Korea.
authors.forename: Hyewon
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Kang
authors.affiliation: Department of Hematology-Oncology, Konkuk University Medical Center, Seoul, Korea.
authors.forename: Mark Hong
authors.initials: MH
authors.lastname: Lee
authors.affiliation: Center for Hematologic Malignancies, National Cancer Center, Goyang, Korea.
authors.forename: Hyeon-Seok
authors.initials: HS
authors.lastname: Eom
authors.affiliation: Department of Internal Medicine, Chonbuk National University School of Medicine, Jeonju, Korea.
authors.forename: Jae-Yong
authors.initials: JY
authors.lastname: Kwak
authors.affiliation: Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea.
authors.forename: Jae Hoon
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Cheolwon
authors.initials: C
authors.lastname: Suh
authors.affiliation: Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Won Seog
authors.initials: WS
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001215:Asparaginase / Q000008:administration & dosage* / Q000009:adverse effects; D059248:Chemoradiotherapy / Q000009:adverse effects; D002945:Cisplatin / Q000008:administration & dosage; D003907:Dexamethasone / Q000008:administration & dosage; D018450:Disease Progression; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D053208:Kaplan-Meier Estimate; D054391:Lymphoma, Extranodal NK-T-Cell / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D009367:Neoplasm Staging; D011879:Radiotherapy Dosage; D020266:Radiotherapy, Conformal; D056910:Republic of Korea; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D005047:Etoposide; D003907:Dexamethasone; D001215:Asparaginase; D002945:Cisplatin; D007069:Ifosfamide; D008727:Methotrexate
keywords: L-asparaginase; concurrent chemoradiotherapy; extranodal NK/T-cell lymphoma, nasal type; methotrexate; treatment