Annals of Oncology Advance Access originally published online on January 22, 2008
Annals of Oncology 2008 19(3):538-544; doi:10.1093/annonc/mdm497
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gastrointestinal tumors |
Dose-escalated CHOEP for the treatment of young patients with aggressive non-Hodgkin's lymphoma: I. A randomized dose escalation and feasibility study with bi- and tri-weekly regimens
1 Hematology and Oncology, University Hospital Göttingen
2 Internal Medicine I, Saarland University Medical School, Homburg
3 Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig
4 Oncology, University Hospitals of Magdeburg, Magdeburg
5 Oncology, University Hospital Münster, Münster
6 Oncology, City Hospital of Karlsruhe, Karlsruhe
7 Oncology, Kliniken Maria-Hilf, Mönchengladbach
8 Helios-Kliniken, Bad Saarow
9 Oncology, Städtische Kliniken Ludwigshafen, Ludwigshafen
10 Department of Internal Medicine, Städtische Kliniken Oldenburg, 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: To determine the maximum tolerated dose of a bi- and tri-weekly combination chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone plus etoposide (CHOEP) regimen without stem-cell support.
Patients and methods: Randomized phase I/II multicenter four-level (cyclophosphamide: 1000–1200–1400–1600 mg/m2; doxorubicin: 55–60–65–70 mg/m2; etoposide: 375–450–525–600 mg/m2) dose escalation study with CHOEP-14 and CHOEP-21 in young patients (18–60 years) with newly diagnosed aggressive non-Hodgkin's lymphoma. Dose-limiting toxicity was defined as thrombocytopenia <80 000/mm3 and leukocytopenia <2500/mm3 on days 16 (CHOEP-14) and 23 (CHOEP-21) or prolonged (>4 days) leukocytopenia (<1000/mm3) or thrombocytopenia (<20 000/mm3).
Results: One hundred and thirty-nine patients (high-CHOEP-14: 47, high-CHOEP-21: 92) were randomly allocated to the study. Maximal tolerated dose was level 2 for CHOEP-14 and level 4 for CHOEP-21. With a less favorable profile of patients in CHOEP-14, 4-year event-free survival was 47.9% after high-CHOEP-14 and 66.2% after high-CHOEP-21, 4-year overall survival 62.1% after high-CHOEP-14 and 73.4% after high-CHOEP-21, respectively.
Conclusion: Significant dose escalations of CHOEP are possible with granulocyte colony-stimulating factor support, with different chemotherapy models favoring the maximally escalated bi- or tri-weekly regimen, respectively. Because a higher total dose can be achieved with six cycles of the tri-weekly compared with the biweekly regimen, CHOEP-21 at dose escalation level 3 was chosen for a nationwide randomized comparison with baseline CHOEP-21 in a subsequent phase III trial.
Key words: aggressive NHL, chemotherapy models, clinical trials, dose escalation
Both authors contributed equally to this manuscript. Received for publication September 18, 2007. Accepted for publication September 21, 2007.