Treatment of patients with advanced or bulky Hodgkin disease with a 12-week doxorubicin, bleomycin, vinblastine, and Dacarbazine-Like chemotherapy regimen followed by extended-field, full-dose radiotherapy

BACKGROUND. This Phase II study was performed in patients with advanced or bulky Hodgkin disease (HD) to evaluate the results of a 7-drug chemotherapy (CT) regimen that was administered over 12 weeks according to 2 randomized modalities followed by high-dose lymph node irradiation. METHODS. From 1990 to 1996,162 patients with HD at clinical stages (CS) I-III with bulky disease (mediastinal mass ratio greater than or equal to 0.45 and/or unilateral or bilateral pelvic plus lumboaortic disease; 86 patients) or CS IV (76 patients) were randomized to receive the same cumulated dose of a CT regimen consisting of epirubicin (240 mg/m(2)), bleomycin (60 mg/m(2)), vinblastine (20 mg/m(2)), vincristine (4 mg/m(2)), cyclophosphamide (4000 mg/m(2)), etoposide (900 mg/m(2)), and methotrexate (180 mg/m(2)) plus methylprednisolone (1500 mg/m(2)) over 12 weeks either every 4 weeks (Arm Y, 79 patients) or every 3 weeks (Arm Z, 83 patients). Patients with disease in complete remission (CR) or partial remission after CT received extended-field lymph node irradiation (involved areas, 40 grays [Gy]; noninvolved areas, 30 Gy). RESULTS. Forty-two percent of patients achieved a post-CT CR, and 86% of patients achieved a CR after the completion of irradiation (there was no difference between Arm Y and Arm Z). Thirty-five patients developed recurrent disease; most of those patients were in post-CT partial remission. The 10-year freedom from first progression rate was 63.9% (there was no difference between Arm Y and Arm Z). Thirty-eight patients died: 24 patients from HD, 3 patients from CT-related early sepsis, 1 patient from radiation-induced pneumonitis, 6 patients from a second malignancy, and 4 patients from causes unrelated to treatment. The overall 10-year survival rate was 76.7%. Survival was slightly higher among patients in Arm Y (83.3%) compared with patients in Arm Z (70.2%; P = 0.12). CONCLUSIONS. No differences were found when the same amount of CT was delivered in three courses or in four courses. In 1997, because most recurrences of the H90-A/B trial occurred in patients who achieved a post-CT partial remission, the authors decided to reinforce the intensity of the initial CT and designed a new randomized study comparing two modalities of more intensive CT plus consolidative radiotherapy (H97-LM trial).