A prospective, multicenter, randomized trial was undertaken to compare the efficacy and toxicity of adriamycin with mitoxantrone within a 6-drug combination chemotherapy regimen for elderly patients (older than 60 years) with highgrade non-Hodgkin lymphoma (HGL) given for a minimum of 8 weeks. A total of 516 previously untreated patients aged older than 60 years were randomized to receive 1 of 2 anthracycline-containing regimens: adriamycin, 35 mg/m 2 intravenously (IV) on day 1 (n ؍ 259), or mitoxantrone, 7 mg/m 2 IV on day 1 (n ؍ 257); with prednisolone, 50 mg orally on days 1 to 14; cyclophosphamide, 300 mg/m 2 IV on day 1; etoposide, 150 mg/m 2 IV on day 1; vincristine, 1.4 mg/m 2 IV on day 8; and bleomycin, 10 mg/m 2 IV on day 8. Each 2-week cycle was administered for a minimum of 8 weeks in the absence of progression. Forty-three patients were ineligible for analysis. The overall and complete remission rates were 78% and 60% for patients receiving PMitCEBO and 69% and 52% for patients receiving PAdriaCEBO (P ؍ .05, P ؍ .12, respectively). Overall survival was significantly better with PMitCEBO than PAdriaCEBO (P ؍ .0067). However, relapse-free survival was not significantly different (P ؍ .16)