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)

Oncotarget. 2016 Dec 20;7(51):85584-85591. doi: 10.18632/oncotarget.11319.

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.

Keywords: L-asparaginase; concurrent chemoradiotherapy; extranodal NK/T-cell lymphoma, nasal type; methotrexate; treatment.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Asparaginase / administration & dosage*
  • Asparaginase / adverse effects
  • Chemoradiotherapy* / adverse effects
  • Cisplatin / administration & dosage
  • Dexamethasone / administration & dosage
  • Disease Progression
  • Disease-Free Survival
  • Drug Administration Schedule
  • Etoposide / administration & dosage
  • Female
  • Humans
  • Ifosfamide / administration & dosage
  • Kaplan-Meier Estimate
  • Lymphoma, Extranodal NK-T-Cell / mortality
  • Lymphoma, Extranodal NK-T-Cell / pathology
  • Lymphoma, Extranodal NK-T-Cell / therapy*
  • Male
  • Methotrexate / administration & dosage
  • Middle Aged
  • Neoplasm Staging
  • Radiotherapy Dosage
  • Radiotherapy, Conformal*
  • Republic of Korea
  • Time Factors
  • Treatment Outcome

Substances

  • Etoposide
  • Dexamethasone
  • Asparaginase
  • Cisplatin
  • Ifosfamide
  • Methotrexate