BEACOPP, a new dose-escalated and accelerated regimen, is at least as effective as COPP/ABVD in patients with advanced-stage Hodgkin's lymphoma: Interim report from a trial of the German Hodgkin's Lymphoma Study Group

Purpose: The HD9 trial aims to evaluate whether moderate dose escalation an d/or acceleration of standard polychemotherapy is beneficial for advanced-s tage Hodgkin's disease (HD). Two variants of a novel bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (B EACOPP) scheme (standard and escalated dose) are compared with cyclophospha mide, vincristine, procarbazine, and prednisone (COPP)/doxorubicin, bleomyc in, vinblastine, and dacarbazine (ABVD). Patients and Methods: The randomized,three-arm trial recruited patients in stages IIB and IIIA with risk factors and stages IIIB and IV. BEACOPP in ba seline dose contains all drug dosages of COPP/ABVD (except vincristine and procarbazine) rearranged in a shorter, 3-week cycle. Escalated BEACOPP uses higher doses of cyclophosphamide, doxorubicin, and etoposide with granuloc yte colony-stimulating factor (G-CSF) support. After eight chemotherapy cyc les, initial bulky and residual disease is irradiated. The trial is monitor ed and analyzed by means of a sequential strategy. Results: An interim analysis with 505 assessable patients and a median foll ow-up of 23 months showed a significant inferiority (according to sequentia l monitoring strategy) of the COPP/ABVD regimen in progression rate and fre edom from treatment failure (FFTF) compared with the pooled results of both BEACOPP variants. The 24-month FFTF rate was 75% for COPP/ABVD and 84% for BEACOPP pooled (P = .034). There was 12% progressive disease with COPP/ABV D and 6% with BEACOPP pooled. Differences in survival were not significant in sequential analysis. The acute toxicity of baseline BEACOPP resembled th at of COPP/ABVD; escalated BEACOPP showed increased but manageable hematolo gic toxicity. Conclusion: Combined with local irradiation, BEACOPP in one o r both variants shows superior disease control compared with COPP/ABVD, wit h acceptable acute toxicity. Further follow-up is required to assess the ef fect of dosage and the effect on survival and late toxicities. (C) 1998 by American Society of Clinical Oncology.