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

Background. Combination chemotherapy consisting of ifosfa-mide, 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-na¨ve stage I/IINTCL were enrolled in a prospective, multicenter, phase II study and received six cycles of IMEP (ifosfamide 1.5 g/m² on days 1-3; methotrextate 30 mg/m² on days 3 and 10; etoposide 100 mg/m² on days 1-3; and prednisolone 60 mg/m² 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.

Conclusion. 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.