Annals of Oncology Advance Access published online on December 6, 2007
Annals of Oncology, doi:10.1093/annonc/mdm514
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 2007 European Society for Medical Oncology
Dose-escalated CHOEP for the treatment of young patients with aggressive non-Hodgkin's lymphoma: II. Results of the randomized high-CHOEP trial of the German High-Grade Non-Hodgkin's Lymphoma Study Group (DSHNHL)
1 Saarland University Medical School, Homburg
2 Institute for Medical Informatics, Statistics and Epidemiology of Leipzig University, Leipzig
3 University Hospital Essen, Essen
4 Evangelisches Diakonie-Krankenhaus, Bremen
5 City Hospital Krefeld, Krefeld
6 Universitätsklinikum Münster, Münster
7 Katharinenhospital Stuttgart, Stuttgart
8 University Hospital Würzburg, Würzburg
9 Städtisches Klinikum Karlsruhe, Karlsruhe
10 Klinikum Mannheim, Heidelberg University, Mannheim
11 University Hospital Göttingen, Göttingen
12 Strahlentherapie, Saarland University Medical School, Homburg
13 Asklepios Klinik St Georg, Hamburg, Germany
* Correspondence to: Dr M. Pfreundschuh, Innere Medizin I, Saarland University Medical School, D-66421 Homburg, Germany. Tel: +49-6841-162-3002; Fax: +49-6841-162-3101; E-mail: inmpfr{at}uniklinikum-saarland.de
Background: The addition of etoposide to combination chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone [etoposide to combination chemotherapy with cyclophosphamide, vincristine and prednisone (CHOEP)] improved outcome of young patients with good-prognosis aggressive lymphoma. To improve results further, the maximal dose-escalated version of CHOEP-21 tolerable without stem-cell support (high CHOEP: cyclophosphamide 1400 mg/m2, doxorubicin 65 mg/m2, vincristine 2 mg, etoposide 175 mg/m2 x3, prednisone 100 mg x5) was compared with CHOEP-21.
Patients and methods: Intention-to-treat analysis of 389 young (18–60 years) patients with good-prognosis (age-adjusted International Prognostic Index = 0, 1) aggressive lymphoma randomized to CHOEP-21 (n = 194) or high CHOEP (n = 195).
Results: There was no difference in 3-year event-free (64% versus 67%; P = 0.734) or overall survival (83% versus 87%; P = 0.849). Neither low-risk nor low-intermediate risk patients benefited from high CHOEP. High CHOEP was more toxic than CHOEP-21 (grades 3 and 4 leukocytopenia 100% versus 87.2%, P < 0.001; thrombocytopenia 80.8% versus 9.6%, P < 0.001; infections 35% versus 11%, P < 0.001; therapy-associated deaths 3.1% versus 0%, P = 0.03).
Conclusion: Dose-escalated CHOEP-21 does not provide clinical benefit for young patients with good-prognosis aggressive lymphomas. Since differences between chemotherapy regimens are compressed by the addition of rituximab, the results of this trial have bearing on strategies aiming to improve outcome of good-prognosis aggressive lymphomas in the rituximab era.
aggressive NHL, chemotherapy models, clinical trials, dose escalation
Both authors contributed equally to this work. Received for publication September 18, 2007. Accepted for publication October 5, 2007.