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

  

Authors:	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. R.
Article Title:	The NHL-15 protocol for aggressive non-Hodgkin's lymphomas: A sequential dose-dense, dose-intense regimen of doxorubicin, vincristine and high-dose cyclophosphamide
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. © 2004 European Society for Medical Oncology.
Keywords:	adolescent; adult; cancer survival; controlled study; treatment outcome; aged; middle aged; survival analysis; major clinical study; prednisone; constipation; neutropenia; paresthesia; doxorubicin; drug efficacy; drug safety; methotrexate; cancer staging; drug megadose; follow up; cancer grading; melanoma; infection; breast cancer; bone marrow suppression; leukopenia; mucosa inflammation; nausea; vomiting; antineoplastic combined chemotherapy protocols; drug administration schedule; risk factors; cyclophosphamide; vincristine; clinical protocol; pneumocystis pneumonia; angiosarcoma; hematuria; age; febrile neutropenia; drug fatality; cancer regression; nonhodgkin lymphoma; lymphoma, non-hodgkin; atherosclerosis; cardiotoxicity; muscle weakness; large cell lymphoma; high risk population; colon disease; hypothyroidism; cancer classification; mesna; parkinson disease; drug dose regimen; heart left ventricle ejection fraction; injections, subcutaneous; infusions, intravenous; granulocyte colony stimulating factor; heart atrium fibrillation; granulocyte colony-stimulating factor; vocal cord paralysis; hemorrhagic cystitis; autonomic neuropathy; larynx disorder; hoarseness; prostate disease; dose-dense; sudden death; aggressive lymphomas; kidney sarcoma; myelodysplasia; non-hodgkin's lymphomas; myocardial disease; hypokinesia; humans; prognosis; human; male; female; priority journal; article; dose-intense; nhl-15; immunoblastic lymphoma
Journal Title:	Annals of Oncology
Volume:	15
Issue:	10
ISSN:	0923-7534
Publisher:	Oxford University Press
Date Published:	2004-10-01
Start Page:	1495
End Page:	1503
Language:	English
DOI:	10.1093/annonc/mdh390
PROVIDER:	scopus
PUBMED:	15367410
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-6944242554&partnerID=40&md5=67daf2b78d41ece8aae4cff830242193
Notes:	Ann. Oncol. -- Cited By (since 1996):11 -- Export Date: 16 June 2014 -- CODEN: ANONE -- Source: Scopus

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