Long-term results of an intensive regimen: VEBEP plus involved-field radiotherapy in advanced Hodgkin's disease

PURPOSE This pilot study was conducted to evaluate the efficacy and toxicity of a n ew intensive drug regimen, combined with involved-nodal-field radiotherapy, in advanced Hodgkin's disease not treated by chemotherapy. PATIENTS AND METHODS From September 1990 to March 1993, 73 evaluable patients with newly diagnos ed stage IIB, III (A and B), and IV (A and B) Hodgkin's disease or who were relapsing after primary subtotal or total nodal irradiation were treated w ith eight cycles of etoposide, epirubicin, bleomycin, cyclophosphamide, and prednisolone (VEBEP) followed by radiotherapy (30-36 Gy) to the nodal site or sites of pretreatment disease. The median duration of follow-up was 68 months. RESULTS The complete remission rate was 94% (95% CI: 86-98). At 6 years, freedom fr om progression and overall survival rates were 78% (95% CI: 68-88) and 82% (95% CI: 73-91), respectively. There was one episode of fatal sepsis after bone marrow aplasia that occurred after VEBEP and extended-field irradiatio n. Hematologic toxicity during chemotherapy was acceptable; without the sup port of growth factors, grade IV leukopenia and grade IV neutropenia, as de termined within cycles, occurred in 38% and 85% of patients, respectively, but was reversible in the vast majority of patients by the day of treatment recycle. No episodes of epidoxorubicin-related cardiomyopathy or symptomat ic pulmonary toxicity were documented. Overt and/or subclinical hypothyroid ism occurred in 38% of cases. Gonadal damage was evident in the large major ity of male patients but reversible in half of them, whereas permanent ster ility was observed in females at least 35 years of age. No secondary leukem ia has been so far detected. DISCUSSION VEBEP followed by involved-nodal-field radiotherapy is an effective treatme nt for chemotherapy-naive Hodgkin's disease and is associated to acceptable rates of acute and intermediate-term toxicity. This intensive regimen, whi ch does not routinely require the support of hematopoietic growth factors a nd can be delivered in an outpatient setting, warrants a prospective compar ison in a randomized trial versus one of the more effective standard-combin ation regimens.