Abstract
Background: The NHL-15 protocol is a novel, dose-intense, dose-dense, sequential chemotherapy program developed to improve outcome in advanced, aggressive non-Hodgkin's lymphomas. Patients and methods: The phase II NHL-15 protocol comprised: (i) induction [doxorubicin 60 mg/m2 i.v. on weeks 1, 3, 5 and 7 plus vincristine 1.4 mg/m2 i.v. (no cap) on weeks 1, 2, 3, 5 and 7]; and (ii) consolidation (cyclophosphamide 3000 mg/m2 i.v. on weeks 9, 11 and 13 plus granulocyte colony-stimulating factor 5 μg/kg subcutaneous on days 3–10 following each cyclophosphamide dose). Patients with aggressive non-Hodgkin's lymphomas (working formulation: intermediate grade or immunoblastic), bulky stage I and stages II–IV, were eligible. Results: There are 165 eligible patients with a 6.9-year median follow-up (range 0.5–141 months) and a median age of 48 years. For the entire group, 72.1% achieved complete remission, and at 5 years disease-free survival was 57.8% and overall survival (OS) was 62.2%. Ideal dose delivery was >90%. Acute and late toxicities of treatment were manageable and acceptable. Toxic death on treatment was 2.4%. When the diffuse large cell lymphoma histologies were grouped according to the International Prognostic Index (IPI), complete remission and OS in the low-intermediate (LI), and high-intermediate (HI) risk groups were improved by 5%–15% compared with historical CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone). This improvement was also noted for LI and HI risk groups in the age-adjusted (aa)IPI analysis for patients ≤60 years of age. Conclusions: The NHL-15 program can be administered safely and effectively to achieve high rates of durable remission when used for the treatment of advanced stage, aggressive, non-Hodgkin's lymphomas. The 5%–15% improvement in 5-year OS compared with historical CHOP, according to the IPI/aaIPI model (in LI and HI risk groups), is encouraging. Further evaluation and prospective testing of the NHL-15 protocol appears to be warranted.