Combination Chemotherapy Followed By Radiation Therapy in Treating Patients With Aggressive Non-Hodgkin's Lymphoma

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.

DISEASE CHARACTERISTICS:

• Histologically confirmed aggressive non-Hodgkin's lymphoma

• Previously untreated disease
• Favorable prognosis

• International Prognostic Index score of 0-1
• No more than 25% marrow involvement

PATIENT CHARACTERISTICS:

Age

• 18 to 60

Performance status

• ECOG 0-3 OR
• Karnofsky 40-100%

Life expectancy

• Not specified

Hematopoietic

• Platelet count at least 100,000/mm^3
• WBC at least 2,500/mm^3

Hepatic

• No active hepatitis infection

Renal

• Not specified

Other

• HIV negative
• Not pregnant or nursing
• No relevant accompanying disease
• No other concurrent malignancy
• No contraindications to any study medications
• No prior noncompliance by patient

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No prior chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy

Surgery

• Not specified

Other

• No other concurrent participation in another treatment study