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.

Abstract

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.

• Authors: L Trümper, C Zwick, M Ziepert, K Hohloch, R Schmits, M Mohren, R Liersch, M Bentz, U Graeven, U Wruck, M Hoffmann, B Metzner, D Hasenclever, M Loeffler, M Pfreundschuh, German High-Grade Non-Hodgkin's Lymphoma Study Group (DSHNHL)
• Journal: Annals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 19 Issue 3 Pg. 538-44 (Mar 2008) ISSN: 1569-8041 [Electronic] England
• PMID: 18212092 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Vincristine
• Etoposide
• Doxorubicin
• Cyclophosphamide
• Prednisolone

Topics

• Adult
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, toxicity)
• Cyclophosphamide (administration & dosage, toxicity)
• Doxorubicin (administration & dosage, toxicity)
• Drug Administration Schedule
• Erythrocyte Transfusion
• Etoposide (administration & dosage, toxicity)
• Feasibility Studies
• Female
• Follow-Up Studies
• Hematologic Diseases (chemically induced, prevention & control)
• Humans
• Lymphoma, Non-Hodgkin (drug therapy)
• Male
• Maximum Tolerated Dose
• Middle Aged
• Platelet Transfusion
• Prednisolone (administration & dosage, toxicity)
• Remission Induction
• Vincristine (administration & dosage, toxicity)