OBJECTIVES:
* Compare the efficacy of standard-dose vs high-dose cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone followed by radiotherapy, in terms of time to treatment failure, in patients with aggressive non-Hodgkin's lymphoma.
* Compare the acute and long-term toxic effects of these regimens in these patients.
* Compare the complete response rate, survival and tumor control, and disease-free survival in patients treated with these regimens.
* Analyze the time to relapse after radiotherapy in these patients.
OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to LDH levels (no greater than upper limit of normal \[ULN\] vs greater than ULN), initial bulky disease (yes vs no), stage (I or II vs II or IV), ECOG performance status (0 or 1 vs 2 or 3), and participating center. Patients are randomized to 1 of 2 treatment arms as follows:
* Arm I (Standard dose): Patients receive cyclophosphamide IV, doxorubicin IV, and vincristine IV on day 1; etoposide IV on days 1-3; and oral prednisone on days 1-5 (CHOEP) in standard doses.
* Arm II (Escalated dose): Patients receive high-dose CHOEP as in arm I. Patients also receive filgrastim (G-CSF) subcutaneously on days 6-12.
In both arms, treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
After completion of CHOEP chemotherapy, patients with initial bulky disease or extranodal involvement undergo radiotherapy 5 days a week for 4 weeks.
Patients who undergo radiotherapy are followed at 2 months after radiotherapy. All patients (including those who undergo radiotherapy) are followed every 3 months for 2 years and then every 6 months for 3 years.
PROJECTED ACCRUAL: A total of 389 patients were accrued for this study.
