Chemotherapy Alone for Early Hodgkin's Lymphoma: An Emerging Option

Abstract

Early stage Hodgkin’s lymphoma is a highly curable disease. Combined chemotherapy and radiation has resulted in high freedom-from-progression rates at 5 to 12 years in the range of 93% for stages I and II patients with asymptomatic presentations and approximately 85% for those with unfavorable disease characteristics. 1-3 The revelation of serious cardiac and second malignancy issues in long-term survivors treated with radiotherapy has prompted a reconsideration of its role when used alone or combined with chemotherapy. Thus, there is a serious need to assess the benefits of chemotherapy alone in patients with early stage disease, especially in those without bulky presentations. In this issue of the Journal of Clinical Oncology is the publication of a trial conducted by the National Cancer Institute of Canada (NCI-C) in collaboration with the Eastern Cooperative Oncology Group (ECOG) addressing the role of chemotherapy alone for early-stage Hodgkin’s lymphoma. 4 The trial was conceived in the early 1990s, when subtotal nodal radiation therapy with splenic irradiation was the standard treatment in Canada for clinically staged patients with early nonbulky stage I to IIA disease. The experimental arm was the chemotherapy regimen of doxorubicin, bleomycin, vincristine and dacarbazine (ABVD) alone for four cycles if a complete response (CR) was achieved after two cycles. Otherwise, patients received six cycles. The standard arm was radiation therapy alone, unless one of the following was present: erythocyte sedimentation rate (ESR) 50 mm/h, or four or more nodal sites, in which case patients received two cycles of ABVD before protocol irradiation. Approximately 70% of 399 total patients had one or two of these unfavorable features. Thus, for a considerable fraction of the patient population, the study was a comparison of combined-modality therapy with chemotherapy alone. At a median follow-up of 4.3 years, freedom from progression (FFP) was the only parameter that reached statistical significance, in which the standard arm had a FFP of 94% compared with 88% for chemotherapy alone (P .04). This difference was confined to the unfavorable group. Further, there were no differences in the event-free and overall survivals. Although the standard arm of this trial is no longer used, subsequent trials have confirmed that combined-modality therapy is superior in FFP compared to radiation alone and that chemotherapy with involved-field radiation therapy is comparable in benefit to more extensive-field radiation plus the same chemotherapy. 5