Comparison of Two Combination Chemotherapy Regimens in Treating Patients With Stage III or Stage IV Hodgkin's Lymphoma

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells. It is not yet known which combination chemotherapy regimen is more effective in treating stage III or stage IV Hodgkin's lymphoma.

PURPOSE: Randomized phase III trial to compare the effectiveness of two combination chemotherapy regimens in treating patients who have stage III or stage IV Hodgkin's lymphoma.

OBJECTIVES:

* Compare event-free survival of patients with stage III or IV Hodgkin's lymphoma treated with bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone vs doxorubicin, bleomycin, vinblastine, and dacarbazine.
* Compare complete response, disease-free survival, and overall survival of patients treated with these regimens.
* Compare quality of life of patients treated with these regimens.
* Compare occurrence of second malignancies in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to International Prognostic Score (3 vs 4 or more) and participating center. Patients are randomized to 1 of 2 treatment arms.

* Arm I (BEACOPP): Patients receive doxorubicin IV over 5 minutes and cyclophosphamide IV on day 1; etoposide IV over 30 minutes on days 1-3; oral procarbazine on days 1-7; oral prednisone on days 1-14; and vincristine IV and bleomycin IV or intramuscularly (IM) on day 8. Patients may receive dexamethasone in place of prednisone. Patients also receive filgrastim (G-CSF) subcutaneously (SC) beginning on day 9 and continuing until blood counts recover or pegfilgrastim SC on day 9 only. Treatment repeats every 22 days for 8 courses (4 courses escalated dose followed by 4 courses baseline dose) in the absence of disease progression or unacceptable toxicity.
* Arm II (ABVD): Patients receive doxorubicin IV over 5 minutes, bleomycin IV or IM, vinblastine IV, and dacarbazine IV over 5-10 minutes on days 1 and 15. Treatment repeats every 28 days for 8 courses in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, at the end of therapy, and then annually for 10 years.

Patients are followed every 3 months for 3 years, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 550 patients (225 per treatment arm) will be accrued for this study within 5.5 years.

Eligibility Criteria:
DISEASE CHARACTERISTICS:

* Histologically confirmed Hodgkin's lymphoma

  * No lymphocyte predominant, nodular type (nodular paragranuloma)
  * Clinical stage III or IV disease
* At least 1 bidimensionally measurable target lesion or extranodal lesion
* International Prognostic Score of at least 3

PATIENT CHARACTERISTICS:

Age

* 16 to 60

Performance status

* WHO 0-2

Life expectancy

* Not specified

Hematopoietic

* WBC greater than 2,000/mm\^3
* Platelet count greater than 100,000/mm\^3

Hepatic

* No prior uncontrolled hepatitis B viral infection
* Bilirubin no greater than 2.5 times normal (unless due to Hodgkin's lymphoma)

Renal

* Creatinine no greater than 2.0 mg/dL (unless due to Hodgkin's lymphoma)

Cardiovascular

* No severe cardiac disease that would limit normal life expectancy or preclude study
* LVEF at least 50%

Pulmonary

* No severe pulmonary disease that would limit normal life expectancy or preclude study
* Respiratory function at least 30%

Other

* HIV negative
* HTLV1 negative
* No severe active infection
* No severe neurological or metabolic disease that would limit normal life expectancy or preclude study
* No other prior or concurrent malignancy except basal cell skin cancer or carcinoma in situ of the cervix
* No psychological, familial, sociological, or geographical condition that would preclude study
* Not pregnant or nursing
* Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

* Not specified

Chemotherapy

* Not specified

Endocrine therapy

* Not specified

Radiotherapy

* No concurrent radiotherapy

Surgery

* Not specified

Other

* No prior therapy for Hodgkin's lymphoma