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


METHODS
The phase II NHL-15 protocol comprised: (i) induction [doxorubicin 60 mg/m(2) i.v. on weeks 1, 3, 5 and 7 plus vincristine 1.4 mg/m(2) i.v. (no cap) on weeks 1, 2, 3, 5 and 7]; and (ii) consolidation (cyclophosphamide 3000 mg/m(2) i.v. on weeks 9, 11 and 13 plus granulocyte colony-stimulating factor 5 microg/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 < or =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.
Portlock
C S
CS
Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA. portlocc@mskcc.org
Qin
J
J
Schaindlin
P
P
Roistacher
N
N
Myers
J
J
Filippa
D
D
Louie
D
D
Zelenetz
A D
AD
O'Brien
J P
JP
Moskowitz
C
C
Norton
L
L
Yahalom
J
J
Straus
D J
DJ
Bertino
J R
JR
D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D007279:Injections, Subcutaneous; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D016019:Survival Analysis; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
D016179:Granulocyte Colony-Stimulating Factor; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide