A prospective clinical trial comparing chemotherapy, radiotherapy and combined therapy in the treatment of early stage Hodgkin's disease with bulky disease. Results of a prospective randomized clinical trial of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by radiation therapy (RT) versus ABVD alone for stages I, II, and IIIA nonbulky Hodgkin disease. Chemotherapy and combined modality therapy for Hodgkin's disease: a progress report on Cancer and Leukemia Group B studies. Randomized trial of chemotherapy versus chemotherapy plus radiotherapy for stage I-II Hodgkin's 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. To determine whether combined modality therapy (CMT) is superior to chemotherapy (CT) alone, 152 untreated Hodgkin disease patients with clinical stages (CSs) IA, IB, IIA, IIB, and IIIA without bulk disease were prospectively randomized to 6 cycles of doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) alone or 6 cycles of ABVD followed by radiation therapy (RT) (3600 cGy: involved field for 11 patients, modified extended field for the rest). Of 76 patients randomized to receive RT, 65 actually received it, and 11 did not (4 progressed, 1 had bleomycin toxicity, 6 refused). For ABVD + RT, the complete remission (CR) percentage was 94% and no major response, 6%. For ABVD alone, 94% achieved a CR; 1.5%, a partial response (PR); and 4.5%, no major response. At 60 months CR duration, freedom from progression (FFP), and overall survival (OS) for ABVD + RT versus ABVD alone are 91% versus 87% (P = .61), 86% versus 81% (P = .61), and 97% versus 90% (P = .08), respectively (log-rank). The 95% confidence intervals for CR duration, FFP, and OS differences at 5 years were -8% to 15%, -8% to 18%, and -4% to 12%, respectively. Although significant differences were not seen, it is possible that a benefit in outcome of less than 20% for CMT might be seen in a larger trial. Between 1974 and 1977, the Cancer and Leukemia Group B (CALGB) initiated four studies which address current major questions in the therapy for Hodgkin's disease. The efficacy of chemotherapy alone as compared with combined modality therapy in patients with poor-prognostic stages I and II is evaluated in CALGB 7751. Currently, both therapies produce very high complete remission rates in asymptomatic patients; the remission rate is better with combined modality therapy in symptomatic patients. Single and combined modality therapies are compared for stage III patients in CALGB 7451. Complete remission rates have been similar, but relapse-free survival is superior for patients treated with local nodal radiotherapy followed by chemotherapy (P = 0.04). In particular, stage IIIA patients with nodular sclerosis seem to benefit from the inclusion of radiotherapy in their initial treatment. In CALGB 7551, the efficacy of chemotherapy alone versus chemotherapy plus radiotherapy to areas of bulky disease is under study in patients with stages IIIB and IV. Currently, a relapse rate of less than 10% has been seen among sites irradiated, and survival is best for patients treated with radiotherapy bracketed by chemotherapy. Finally, the role of two alternating non-cross-resistant combination chemotherapy programs is being studied in CALGB 7552. Relapse-free and overall survival is better with the doxorubicin-containing regimen than with either the alternating or alternate chemotherapy program. At present, the median followup for each of these studies is less than 5 years. Further observation is required to answer the critical questions relating to prolonged disease-free survival and cure. A total of 277 patients with untreated Hodgkin's disease, clinical stages I-II, were randomized to cyclophosphamide, vinblastine, procarbazine, and prednisone (CVPP) alone for 6 monthly cycles or to CVPP plus radiation therapy (RT), 3,000 rad, to involved areas (CVPP plus RT). One or more of the following factors were considered as unfavorable prognosis: age greater than 45 years, more than two lymph node areas involved, or bulky disease. In the favorable group, disease-free survival (77% vs. 70%) or overall survival (92% vs. 91%) at 84 months for CVPP versus RT plus CVPP was similar. Patients with unfavorable prognosis treated with RT plus CVPP had longer disease-free survival (75% vs. 34%) (P = .001) and overall survival (84% vs. 66%) than patients treated with CVPP alone.
Adding radiotherapy to chemotherapy improves tumour control and overall survival in patients with early stage Hodgkin lymphoma.