A randomized phase II study of CEOP with or without semustine as induction chemotherapy in patients with stage IE/IIE extranodal NK/T-cell lymphoma, nasal type in the upper aerodigestive tract.

In this randomized phase II study, we evaluated the efficacy of semustine added to CEOP regimen as induction chemotherapy in patients with stage I(E)/II(E) extranodal NK/T-cell lymphoma, nasal type in the upper aerodigestive tract. Seventy-five eligible patients were randomized to receive either CEOP or CEOP plus semustine followed by involved-field radiotherapy. The overall response rate of induction chemotherapy was 57.9% in CEOP arm compared with 62.2% in CEOP plus semustine arm (P=0.71). With a median follow-up of 30.1 months, 2-year overall survival was 73.3% and 62.2%, respectively (P=0.37). Toxicities in both arms were comparable and manageable. Through univariate and multivariate analysis, PS of 2, Stage II(E) and elevated LDH level were identified to be adverse prognostic factors. A new prognostic index categorized three groups of patients (low risk, no adverse factors; intermediate risk, one factor; and high risk, 2 or 3 factors) with highly significant difference of prognosis. Two-year overall survival was 87.5%, 60.6% and 30%, respectively (P=0.0002). The addition of semustine to CEOP regimen was not associated with improved efficacy. More effective treatment needs to be explored in patients with intermediate or high risk.