OBJECTIVES:

• Compare the effect of chlorambucil vs involved-field radiotherapy on progression-free survival of patients with previously untreated stage III or IV follicular lymphoma.
• Compare the complete and partial remission rates and overall survival of patients treated with these regimens.
• Compare the toxicity of these regimens in these patients.
• Compare the quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral chlorambucil on days 1-5. Treatment repeats every 4 weeks for 6-8 courses in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients undergo radiotherapy on days 1 and 3 (and days 15 and 17 for split course).

Quality of life is assessed at baseline, prior to course 3, 6, and 8 (arm I), and then at 4-6 weeks after study.

Patients are followed at 4-6 weeks, 3-4 months (arm I), 3 months and 6 months (arm II), 11, 12, 15, 18, and 21 months, and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 444 patients (222 per treatment arm) will be accrued for this study within 4 years.

DISEASE CHARACTERISTICS:

• Diagnosis of follicular lymphoma

  • Stage III or IV disease
  • Grades I, II, or III
  • Previously untreated disease
• Nodal and extranodal sites
• Bidimensionally measurable disease by physical examination or diagnostic imaging
• No CNS or orbital non-Hodgkin's lymphoma localization

PATIENT CHARACTERISTICS:

Age:

• 18 and over (for patients at EORTC centers)
• 65 and over (for patients at HOVON centers)

Performance status:

• WHO 0-2

Life expectancy:

• Not specified

Hematopoietic:

• WBC at least 4,000/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 6.0 g/dL

Hepatic:

• Not specified

Renal:

• Not specified

Cardiovascular:

• No severe cardiac disease that would preclude study treatment

Pulmonary:

• No severe pulmonary disease that would preclude study treatment

Other:

• HIV negative
• No severe neurologic, psychiatric, or metabolic disease that would preclude study treatment
• No other prior malignancy except basal cell skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• Not specified

Endocrine therapy:

• No concurrent systemic corticosteroids, including dexamethasone for nausea and vomiting palliation (inhalation and topical corticosteroids allowed)

Radiotherapy:

• No concurrent elective radiotherapy to an adjacent negative lymph node

Surgery:

• Not specified