Annals of Oncology Advance Access originally published online on December 6, 2007
Annals of Oncology 2008 19(3):545-552; doi:10.1093/annonc/mdm514
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hematologic malignancies |
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.
Key words: 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.