RATIONALE: Imaging procedures, such as fludeoxyglucose F 18 (FDG)-PET/CT scan, done before, during, and after chemotherapy may help doctors assess a patient's response to treatment and help plan the best treatment. It is not yet known whether FDG-PET/CT imaging is effective in assessing response to chemotherapy in patients with newly diagnosed Hodgkin lymphoma.

PURPOSE: This randomized phase III trial is studying FDG-PET/CT imaging to see how well it works in assessing response to chemotherapy in patients with newly diagnosed stage II, stage III, or stage IV Hodgkin lymphoma.

OBJECTIVES:

• To determine if fludeoxyglucose F 18 (FDG)-PET/CT imaging can be reproducibly and effectively applied in the early assessment of response to chemotherapy in patients with newly diagnosed stage II-IV Hodgkin lymphoma.
• To determine if a negative FDG-PET/CT scan after 2 courses of ABVD chemotherapy comprising doxorubicin hydrochloride, bleomycin, vinblastine, and dacarbazine can be used to predict a group of patients for whom it is safe to reduce therapy by the subsequent omission of bleomycin, without detriment to progression-free survival.
• To determine if treatment intensification in response to positive FDG-PET/CT imaging after 2 courses of ABVD chemotherapy can improve the outcome by comparison with previous series.

OUTLINE: This is a multicenter study.

Patients undergo fludeoxyglucose F 18 (FDG)-PET/CT imaging at baseline. Patients then receive ABVD chemotherapy comprising doxorubicin hydrochloride IV, bleomycin IV, vinblastine IV, and dacarbazine IV on days 1 and 15. Treatment repeats every 28 days for up to 2 courses in the absence of disease progression or unacceptable toxicity. Between days 22 and 25 of course 2, patients undergo a second FDG-PET/CT scan to assess response. Subsequent therapy is based on FDG-PET/CT scan results.

• Negative FDG-PET/CT scan: Patients with a negative FDG-PET/CT scan are randomized to 1 of 2 treatment arms.
  • Arm I (ABVD chemotherapy): Patients receive ABVD chemotherapy comprising doxorubicin hydrochloride IV, bleomycin IV, vinblastine IV, and dacarbazine IV on days 1 and 15. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
  • Arm II (AVD chemotherapy): Patients receive AVD chemotherapy comprising doxorubicin hydrochloride IV, vinblastine IV, and dacarbazine IV on days 1 and 15. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
• Positive FDG-PET/CT scan: Patients with a positive FDG-PET/CT scan are assigned to 1 of 2 chemotherapy regimens, as determined by the participating center.
  • BEACOPP-14 chemotherapy: Patients receive doxorubicin hydrochloride IV and cyclophosphamide IV on day 1; etoposide IV on days 1-3; oral procarbazine hydrochloride and oral prednisolone on days 1-7; and bleomycin IV and vincristine IV on day 8. Patients also receive filgrastim (G-CSF) subcutaneously (SC) on days 8-13 OR pegfilgrastim SC once on day 8. Treatment repeats every 14 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
  • BEACOPP-escalated chemotherapy: Patients receive doxorubicin hydrochloride IV and cyclophosphamide IV on day 1; etoposide IV on days 1-3; oral procarbazine hydrochloride on days 1-7; oral prednisolone on days 1-14; and bleomycin IV and vincristine IV on day 8. Patients also receive G-CSF SC beginning on day 8 and continuing until blood counts recover OR pegfilgrastim SC once on day 8. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.

After completion of BEACOPP chemotherapy, patients undergo a third FDG-PET/CT scan to assess response. Patients with a negative FDG-PET/CT scan receive 2 more courses of BEACOPP-14 or 1 more course of BEACOPP-escalated chemotherapy. Patients with a persistently positive FDG-PET/CT scan may receive radiotherapy to sites of FDG uptake or salvage chemotherapy, at the investigator's discretion.

After completion of study therapy, patients are followed every 3 months for 1 year, every 4 months for 2 years, every 6 months for 2 years, and then annually thereafter.

Peer Reviewed and Funded or Endorsed by Cancer Research UK.

DISEASE CHARACTERISTICS:

• Histologically confirmed classical Hodgkin lymphoma (HL) meeting the following criteria:
  • Meets current WHO classification criteria (i.e., nodular sclerosis, mixed cellularity, lymphocyte rich, and lymphocyte-depleted)
  • Clinical stage IIB, III, or IV disease OR clinical stage IIA disease with adverse features, including any of the following:
    • Bulk mediastinal disease, defined as maximal transverse diameter of mass > 0.33 of the internal thoracic diameter at D5/6 interspace on routine chest x-ray
    • Disease outside the mediastinum and lymph node or lymph node mass > 10 cm in diameter
    • More than two sites of disease
    • Other poor-risk features that require treatment with full course combination chemotherapy
• Newly diagnosed disease
• No CNS or meningeal involvement by lymphoma

PATIENT CHARACTERISTICS:

• ECOG performance status 0-3
• Life expectancy > 3 months
• ANC > 1,500/mm^3 (unless there is bone marrow infiltration by lymphoma)
• Platelet count > 100,000/mm^3 (unless there is bone marrow infiltration by lymphoma)
• Creatinine < 150% of upper limit of normal (ULN)
• Bilirubin < 2.0 times ULN (unless attributed to lymphoma)
• Transaminases < 2.5 times ULN (unless attributed to lymphoma)
• LVEF ≥ 50% (in patients with a significant history of ischemic heart disease or hypertension)
• Diffusion capacity within 25% of normal predicted value by lung function testing
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Amenable to the administration of a full course of chemotherapy, according to the investigator
• Must have access to PET/CT scanning
• No poorly controlled diabetes mellitus
• No cardiac contraindication to doxorubicin hydrochloride, including abnormal contractility by ECHO or MUGA
• No neurological contraindication to chemotherapy (e.g., pre-existing neuropathy)
• No other concurrent uncontrolled medical condition
• No other active malignant disease within the past 10 years, except fully excised basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the uterine cervix
• No known positivity for HIV, hepatitis B surface antigen, or hepatitis C
  • Routine testing, in the absence of risk factors, is not required
• No medical or psychiatric condition that compromises the patient's ability to give informed consent

PRIOR CONCURRENT THERAPY:

• No prior chemotherapy, radiotherapy or other investigational drug for HL