The NHL-15 protocol for aggressive non-Hodgkin's lymphomas: A sequential dose-dense, dose-intense regimen of doxorubicin, vincristine and high-dose cyclophosphamide

C. S. Portlock, J. Qin, P. Schaindlin, N. Roistacher, J. Myers, D. Filippa, D. Louie, A. D. Zelenetz, J. P. O'Brien, C. Moskowitz, L. Norton, J. Yahalom, D. J. Straus, Joseph Bertino

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13 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1495-1503
Number of pages9
JournalAnnals of Oncology
Volume15
Issue number10
DOIs
StatePublished - Oct 2004

All Science Journal Classification (ASJC) codes

  • Hematology
  • Oncology

Keywords

  • Aggressive lymphomas
  • Dose-dense
  • Dose-intense
  • NHL-15
  • Non-Hodgkin's lymphomas

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    Portlock, C. S., Qin, J., Schaindlin, P., Roistacher, N., Myers, J., Filippa, D., Louie, D., Zelenetz, A. D., O'Brien, J. P., Moskowitz, C., Norton, L., Yahalom, J., Straus, D. J., & Bertino, J. (2004). The NHL-15 protocol for aggressive non-Hodgkin's lymphomas: A sequential dose-dense, dose-intense regimen of doxorubicin, vincristine and high-dose cyclophosphamide. Annals of Oncology, 15(10), 1495-1503. https://doi.org/10.1093/annonc/mdh390