Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)

Drug combinations described in this section:

• ABVD: doxorubicin plus bleomycin plus vinblastine plus dacarbazine.
• BEACOPP: bleomycin plus etoposide plus doxorubicin plus cyclophosphamide plus vincristine plus procarbazine plus prednisone.
• COPP/ABVD: cyclophosphamide plus vincristine plus procarbazine plus prednisone/doxorubicin plus bleomycin plus vinblastine plus dacarbazine.
• MOPP: mechlorethamine plus vincristine plus procarbazine plus prednisone.
• MOPP alternating with ABVD: mechlorethamine plus vincristine plus procarbazine plus prednisone alternating with doxorubicin plus bleomycin plus vinblastine plus dacarbazine.
• MOPP/ABV hybrid: mechlorethamine plus vincristine plus procarbazine plus prednisone/doxorubicin plus bleomycin plus vinblastine.
• Stanford V: doxorubicin plus vinblastine plus mechlorethamine plus etoposide plus vincristine plus bleomycin plus prednisone.

Patients are designated as having advanced unfavorable Hodgkin lymphoma (HL) if they have clinical stage III or stage IV disease and four or more risk factors on the International Prognostic Index for HL, which corresponds to a freedom-from-progression at worse than 50% at 5 years with combination chemotherapy. [1]

ABVD therapy for 6 to 8 months is as effective as 12 months of MOPP alternating with ABVD, and both are superior to MOPP alone in terms of FFS (50% vs. 36% with a 14-year median follow-up; P=.03). [2] [3] [ Level of evidence: 1iiA] The Intergroup trial comparing ABVD with MOPP/ABV hybrid showed equivalent efficacy in FFS and overall survival (OS), but increased toxic effects in the hybrid arm, especially from second malignancies. [4] [ Level of evidence: 1iiA]

The German Hodgkin Lymphoma Study Group randomly assigned 1,201 patients with advanced-stage disease to COPP/ABVD, BEACOPP, or to increased-dose BEACOPP, with most patients receiving consolidative radiation therapy to sites of initial bulky disease (≥5 cm). [5] The 5-year OS was 83% for COPP/ABVD, 88% for BEACOPP, and 91% for increased-dose BEACOPP ( P=.16 for the comparison of COPP/ABVD with BEACOPP, P=.06 for the comparison of BEACOPP with increased-dose BEACOPP, and P=.002 for the comparison of COPP/ABVD with increased-dose BEACOPP). [5] [ Level of evidence: 1iiA] The actuarial rate of secondary acute leukemias 5 years after diagnosis of HL was 0.4% for COPP/ABVD, 0.6% for BEACOPP, and 2.5% for increased-dose BEACOPP ( P=.03). Stanford V is an alternative drug combination currently under clinical evaluation with the Eastern Cooperative Oncology Group (ECOG) and the European Organization for Research and Treatment of Cancer (EORTC) in the ECOG-2496and the EORTC-20012trials, respectively. [6]

Three prospective randomized trials did not show a benefit in OS from the addition of consolidative radiation therapy to chemotherapy for patients with advanced-stage disease. [7] [8] [9] [ Level of evidence: 1iiA] In a meta-analysis of 1,740 patients treated on 14 different trials, no improvement was observed in 10-years’ OS for patients with advanced-stage HL who received combined modality therapy versus chemotherapy alone. [10] [ Level of evidence: 3iiiA] No survival advantage is known for the use of radiation consolidation for patients with massive mediastinal disease and advanced stage, though differences exist in sites of first relapse. [11]

Clinical trials are addressing the role of more intensive regimens for patients with advanced-stage disease and poor prognostic factors. Controversy exists about whether the optimal strategy should involve early dose intensification, with subsequent risks of increased late toxic effects (such as leukemia) or whether ABVD should be employed and patients who relapse be salvaged with high-dose treatment and autografting. In a prospective randomized trial of 163 patients with unfavorable advanced-stage disease who attained a complete or partial remission after four cycles of ABVD, no difference was observed in OS or FFS either with high-dose therapy with autologous stem cell transplant or with four more cycles of ABVD. [12] [ Level of evidence: 1iiA]

Treatment options:

• ABVD for six to eight cycles.
• BEACOPP (increased dose).