title: Phase II study of SMILE chemotherapy for newly diagnosed stage IV, relapsed, or refractory extranodal natural killer (NK)/T-cell lymphoma, nasal type: the NK-Cell Tumor Study Group study.
abstract: OBJECTIVE
  To explore a more effective treatment for newly diagnosed stage IV, relapsed, or refractory extranodal natural killer/T-cell lymphoma, nasal type (ENKL), we conducted a phase II study of the steroid (dexamethasone), methotrexate, ifosfamide, L-asparaginase, and etoposide (SMILE) regimen.
  
  
  METHODS
  Patients with newly diagnosed stage IV, relapsed, or refractory disease and a performance status of 0 to 2 were eligible. Two cycles of SMILE chemotherapy were administered as the protocol treatment. The primary end point was the overall response rate (ORR) after the protocol treatment.
  
  
  RESULTS
  A total of 38 eligible patients were enrolled. The median age was 47 years (range, 16 to 67 years), and the male:female ratio was 21:17. The disease status was newly diagnosed stage IV in 20 patients, first relapse in 14 patients, and primary refractory in four patients. The eligibility was revised to include lymphocyte counts of 500/μL or more because the first two patients died from infections. No treatment-related deaths were observed after the revision. The ORR and complete response rate after two cycles of SMILE chemotherapy were 79% (90% CI, 65% to 89%) and 45%, respectively. In the 28 patients who completed the protocol treatment, 19 underwent hematopoietic stem-cell transplantation. The 1-year overall survival rate was 55% (95% CI, 38% to 69%). Grade 4 neutropenia was observed in 92% of the patients. The most common grade 3 or 4 nonhematologic complication was infection (61%).
  
  
  CONCLUSIONS
  SMILE chemotherapy is an effective treatment for newly diagnosed stage IV, relapsed or refractory ENKL. Myelosuppression and infection during the treatment should be carefully managed.
authors: Mie University Graduate School of Medicine, Tsu, Japan.
authors: Motoko
authors: M
authors: Yamaguchi
authors: Yok-Lam
authors: YL
authors: Kwong
authors: Won Seog
authors: WS
authors: Kim
authors: Yoshinobu
authors: Y
authors: Maeda
authors: Chizuko
authors: C
authors: Hashimoto
authors: Cheolwon
authors: C
authors: Suh
authors: Koji
authors: K
authors: Izutsu
authors: Fumihiro
authors: F
authors: Ishida
authors: Yasushi
authors: Y
authors: Isobe
authors: Eisaburo
authors: E
authors: Sueoka
authors: Junji
authors: J
authors: Suzumiya
authors: Takao
authors: T
authors: Kodama
authors: Hiroshi
authors: H
authors: Kimura
authors: Rie
authors: R
authors: Hyo
authors: Shigeo
authors: S
authors: Nakamura
authors: Kazuo
authors: K
authors: Oshimi
authors: Ritsuro
authors: R
authors: Suzuki
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001215:Asparaginase / Q000008:administration & dosage; D005260:Female; D006801:Humans; D054391:Lymphoma, Extranodal NK-T-Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009669:Nose Neoplasms / Q000188:drug therapy* / Q000473:pathology; D012008:Recurrence
chemical_list: D001215:Asparaginase