A prospective clinical trial comparing chemotherapy, radiotherapy and combined therapy in the treatment of early stage Hodgkin's disease with bulky disease.

We performed a randomized clinical trial to assess the usefulness and toxicity of combined therapy compared with chemotherapy and radiotherapy in the treatment of early stage Hodgkin's disease with bulky disease as an adverse prognostic factor. Three-hundred and seven patients were enrolled into the study. They were randomized to receive either radiotherapy (extended field, generally mantle, 3500 cGy), or chemotherapy (adriamycin, bleomicin, vinblastine and dacarbazine: ABVD, 6 monthly) cycles or combined therapy (three cycles of ABVD, followed by irradiation therapy and three more cycles of chemotherapy). The median follow-up duration from start of treatment was 11.4 years. Complete response rates were similar in the three arms: 83% for radiotherapy (95% confidence interval [CI] 67-92%), 80% for chemotherapy (CI 69-88%) and 87% for combined therapy (CI 74-94%). However, disease-free survival and overall survival were better in the patients treated with combined therapy. At 12 years 76% (CI 51-93%) of the patients treated with combined therapy remained alive in the first complete remission compared with 42% (CI 26-61%) in patients treated with radiotherapy and 48% (CI 31-57%) in patients who had received chemotherapy alone (P < 0.01). Improvement in overall survival was also evident at 12 years: 88% (CI 59-93%) in those who had received combined therapy, compared with 53% (CI 36-67%) in the radiotherapy arm and 59% (CI 35-67%) in the chemotherapy group. Acute toxicity was more frequent in patients treated with combined therapy, but no death related treatment was observed in the three groups. Late toxicity was similar in the three treatment groups. Combined therapy with extended field radiotherapy and six cycles of chemotherapy is an effective treatment of patients with early stage bulky Hodgkin's disease compared with chemotherapy or radiotherapy alone.