title: A phase II study of ifosfamide, methotrexate, etoposide, and prednisolone for previously untreated stage I/II extranodal natural killer/T-cell lymphoma, nasal type: a multicenter trial of the Korean Cancer Study Group.
abstract: BACKGROUND
  Combination chemotherapy consisting of ifosfamide, methotrexate, etoposide, and prednisolone (IMEP) was active as first-line and second-line treatment for extranodal natural killer/T-cell lymphoma (NTCL).
  
  
  METHODS
  Forty-four patients with chemo-naïve stage I/II NTCL were enrolled in a prospective, multicenter, phase II study and received six cycles of IMEP (ifosfamide 1.5 g/m(2) on days 1-3; methotrextate 30 mg/m(2) on days 3 and 10; etoposide 100 mg/m(2) on days 1-3; and prednisolone 60 mg/m(2) per day on days 1-5) followed by involved field radiotherapy (IFRT).
  
  
  RESULTS
  Overall response rates were 73% (complete remission [CR] in 11 of 41 evaluable patients [27%]) after IMEP chemotherapy and 78% (CR 18 of 27 evaluable patients [67%]) after IMEP followed by IFRT. Neutropenia and thrombocytopenia were documented in 33 patients (75%) and 7 patients (16%), respectively. Only 8 patients (18%) experienced febrile neutropenia. Three-year progression-free survival (PFS) and overall survival (OS) were 66% and 56%, respectively. High Ki-67 (≥70%) and Ann Arbor stage II independently reduced PFS (p = .004) and OS (p = .001), respectively.
  
  
  CONCLUSIONS
  Due to the high rate of progression during IMEP chemotherapy, IFRT needs to be introduced earlier. Moreover, active chemotherapy including an l-asparaginase-based regimen should be use to reduce systemic treatment failure in stage I/II NTCL.
authors.affiliation: Seoul National University Hospital, Seoul, Republic of Korea;
authors.forename: Tae Min
authors.initials: TM
authors.lastname: Kim
authors.affiliation: Seoul National University Hospital, Seoul, Republic of Korea;
authors.forename: Dong-Wan
authors.initials: DW
authors.lastname: Kim
authors.affiliation: Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea;
authors.forename: Yoon-Koo
authors.initials: YK
authors.lastname: Kang
authors.affiliation: Pusan National University Hospital, Busan, Republic of Korea;
authors.forename: Jooseop
authors.initials: J
authors.lastname: Chung
authors.affiliation: Keimyung University Dongsan Medical Center, Daegu, Republic of Korea;
authors.forename: Hong-Suk
authors.initials: HS
authors.lastname: Song
authors.affiliation: Hallym University Sacred Heart Hospital, Seoul, Republic of Korea;
authors.forename: Hyo Jung
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Korea University Medical Center, Seoul, Republic of Korea;
authors.forename: Byung Soo
authors.initials: BS
authors.lastname: Kim
authors.affiliation: Seoul National University Bundang Hospital, Gyeonggi-do, Republic of Korea;
authors.forename: Jong-Seok
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Ulsan University Hospital, Ulsan, Republic of Korea;
authors.forename: Hawk
authors.initials: H
authors.lastname: Kim
authors.affiliation: Korea Cancer Center Hospital, Seoul, Republic of Korea;
authors.forename: Sung Hyun
authors.initials: SH
authors.lastname: Yang
authors.affiliation: Inje University Sanggye Paik Hospital, Seoul, Republic of Korea;
authors.forename: Young Jin
authors.initials: YJ
authors.lastname: Yuh
authors.affiliation: Daegu Catholic University Medical Center, Daegu, Republic of Korea;
authors.forename: Sung Hwa
authors.initials: SH
authors.lastname: Bae
authors.affiliation: Yeungnam University College of Medicine, Daegu, Republic of Korea.
authors.forename: Myung Soo
authors.initials: MS
authors.lastname: Hyun
authors.affiliation: Seoul National University Hospital, Seoul, Republic of Korea;
authors.forename: Yoon Kyung
authors.initials: YK
authors.lastname: Jeon
authors.affiliation: Seoul National University Hospital, Seoul, Republic of Korea;
authors.forename: Chul Woo
authors.initials: CW
authors.lastname: Kim
authors.affiliation: Seoul National University Hospital, Seoul, Republic of Korea; heo1013@snu.ac.kr.
authors.forename: Dae Seog
authors.initials: DS
authors.lastname: Heo
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D018572:Disease-Free Survival; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D007694:Killer Cells, Natural / Q000473:pathology; D016399:Lymphoma, T-Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D009669:Nose Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy; D011239:Prednisolone / Q000008:administration & dosage; D056910:Republic of Korea; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D005047:Etoposide; D011239:Prednisolone; D007069:Ifosfamide; D008727:Methotrexate