RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some find cancer cells and kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin, vincristine, and prednisone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving rituximab together with combination chemotherapy may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving rituximab together with combination chemotherapy works in treating older patients with previously untreated B-cell lymphoma.

OBJECTIVES:

Primary

• Determine a pharmacokinetic profile for pharmacokinetics-based or rituximab within a CHOP-14 regimen comprising cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone in elderly patients with previously untreated aggressive B-cell lymphoma.
• To determine whether increased single-doses of rituximab for males can compensate their lower serum levels.
• Evaluate the safety and toxicity profile of this regimen in male patients.

Secondary

• Determine the rate of complete responses, primary progressions under therapy, event-free survival, progression-free survival, and overall survival in patients treated with this regimen.
• Determine the rate of primary progression in patients treated with this regimen.

OUTLINE: This is a multicenter study. All patients undergo the following treatment.

• Prephase treatment: Patients receive vincristine subcutaneously on day -6 and oral prednisone on days -6 to 0.
• Immunochemotherapy and radiotherapy: Patients receive CHOP chemotherapy comprising cyclophosphamide IV over 15 minutes, doxorubicin hydrochloride IV, and vincristine IV on day 1 and oral prednisone once daily on days 1-5. Patients also receive pegfilgrastim subcutaneously on days 4, 18, 32, 46, 60, and 74. Treatment with CHOP chemotherapy repeats every 14 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who show no response after course 4 of CHOP chemotherapy proceed to salvage chemotherapy off study.

Patients are evaluated 2-4 weeks after completion of CHOP. Patients with initial bulky disease (i.e., diameter ≥ 7.5 cm) or extranodal involvement AND achieving complete remission (CR), unconfirmed CR (CRu), or partial remission undergo radiotherapy 5 days a week for 4 weeks. Patients who do not achieve CR or CRu 2 months after completion of radiotherapy proceed to salvage chemotherapy off study.

Patients are then stratified according to center, International Prognostic Index (1-2 vs 3-5), disease involvement (bulky vs extranodal vs bulky and/or extranodal), age (61-70 years old vs 71-80 years old), and gender. Patients are randomized to 1 of 2 treatment arms.

• Arm I (2-weekly rituximab): Patients receive rituximab IV 375 mg/m^2 (females) and 500 mg/m^2 (males) over 4 hours on days 0, 14, 28, 42, 56, 70, 84, and 98. Patients also receive pegfilgrastim subcutaneously on day 4 of each course.
• Arm II (pharmacokinetic-based dose-dense rituximab): Patients receive rituximab IV 375 mg/m^2 (females) and 500 mg/m^2 (males) over 4 hours on days -1, 0, 3, 7, 14, 21, 28, and 42. Patients also receive pegfilgrastim subcutaneously on day 4 of each course.

Some patients undergo blood sample collection periodically during and after treatment for pharmacokinetic studies.

After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 3 years, and then once a year therafter.

DISEASE CHARACTERISTICS:

• Histological diagnosis of aggressive B-cell lymphoma

  • Previously untreated disease
  • Stage I-IV disease

• CD20-positive disease

• Any International Prognostic Index (IPI) score

• No secondary lymphoma after prior chemotherapy or radiotherapy

• No primary CNS lymphoma

• No primary gastrointestinal (MALT) lymphoma

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Life expectancy ≥ 3 months
• AST and ALT ≤ 3 times normal unless related to lymphoma
• Bilirubin ≤ 2 mg/dL unless related to lymphoma
• Creatinine ≤ 2 times normal unless related to lymphoma
• Fertile patients must use effective contraception
• No known allergic reactions against foreign proteins
• No active infections requiring systemically administered antibiotics or antiviral medications
• No noncompensated heart failure
• No dilatative cardiomyopathy
• No coronary heart disease with ST-segment depression in ECG
• No myocardial infarction during the past 6 months
• No chronic lung disease with hypoxemia
• No severe noncompensated hypertension
• No severe noncompensated diabetes mellitus
• No clinical signs of cerebral dysfunction
• No severe psychiatric disease
• No known HIV infection
• No active chronic hepatitis B or C infection
• No other concurrent diseases that exclude the administration of therapy as outlined by the study protocol

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• More than 12 weeks since prior clinical trial participation
• No prior participation in this study
• No prior therapy, including murine antibody, for this cancer
• No prior organ transplantation
• No concurrent response-adapted radiotherapy ("iceberg radiotherapy")
• No other concurrent anticancer chemotherapy or other study medication