Combination Chemotherapy With or Without Radiation Therapy in Treating Patients With Hodgkin's Lymphoma

OBJECTIVES:

- Compare the failure-free survival of patients with locally extensive or advanced
Hodgkin's lymphoma treated with doxorubicin, bleomycin, vinblastine, and dacarbazine
(ABVD) vs doxorubicin, vinblastine, vincristine, bleomycin, mechlorethamine, etoposide,
and prednisone (Stanford V) with or without radiotherapy.

- Compare the overall survival and freedom from progression in these patients at 5 and 10
years after treatment with these regimens.

- Compare pulmonary function, incidence of second cancers, reproductive function, and
deaths from causes other than Hodgkin's lymphoma in patients treated with these
regimens.

OUTLINE: This is a randomized study. Patients are stratified according to number of adverse
risk factors (0-2 vs 3-7), disease characteristics (locally extensive vs advanced) and time
of entry (before addendum 6 vs. after addendum 6). Patients are randomized to 1 of 2
treatment arms.

- Arm A (ABVD): Patients receive doxorubicin (25 mg/m²), bleomycin (10 u/m²), vinblastine
(6 mg/m²), and dacarbazine (375 mg/m²) IV on days 1 and 15. Courses repeat every 28
days. Patients are restaged after 4 courses. Patients who are in complete remission
receive 2 additional courses. Patients with a partial response or less are evaluated
after 6 courses, and if there is an ongoing response, patients may receive 2 additional
courses for a total of 8. If no ongoing response is observed, patients are removed from
the study. All patients with massive mediastinal disease, regardless of stage, receive
radiotherapy 2-3 weeks after completion of chemotherapy.

- Arm B (Stanford V): Patients receive Stanford V chemotherapy comprising doxorubicin (25
mg/m²) and vinblastine (6 mg/m²) IV on day 1 of weeks 1, 3, 5, 7, 9, and 11; vincristine
(1.4 mg/m²) and bleomycin (5 u/m²) IV on day 1 of weeks 2, 4, 6, 8, 10, and 12;
mechlorethamine (6 mg/m²) IV on day 1 of weeks 1, 5, and 9 (if mechlorethamine is
unavailable, may substitute with cyclophosphamide [375 mg/m²] IV); etoposide (60 mg/m²)
IV on days 1 and 2 of weeks 3, 7, and 11; and oral prednisone (40 mg/m²) every other day
of weeks 1-9 followed by a taper. All patients with bulky disease receive radiotherapy
2-3 weeks after completion of chemotherapy.

Patients are followed every 2 months for 1 year, every 3 months for 1 year, every 4 months
for 1 year, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 850 patients will be accrued for this study within 4.3 years.

Inclusion criteria:

- Histologically proven previously untreated classical Hodgkin's lymphoma

- The following stages are eligible:

- Locally extensive: Stage I-IIA/B with massive mediastinal adenopathy

- Advanced: Stage III or IV

- Measurable or evaluable disease

- Age of 16 and over

- ECOG Performance status 0-2

- Disease-free of prior invasive malignancies for >5 years with the exception of
curatively-treated basal cell or squamous cell carcinoma of the skin or carcinoma in
situ of the cervix

- White blood cell (WBC) at least 4,000/mm³, (unless documented bone marrow involvement)

- Platelet count at least 100,000/mm³ (unless documented bone marrow involvement)

- Bilirubin no greater than 5.0 mg/dL

- Creatinine no greater than 2.0 mg/dL

- Ejection fraction determination recommended if over age 50 and/or have a history of
cardiac disease

- Fertile patients must use effective contraception

- Prior corticosteroids allowed

- Prior surgery allowed

Exclusion criteria:

- Pregnant or nursing

- Prior radiotherapy

- Prior chemotherapy

- Human immunodeficiency virus (HIV) positive