This report aims to assess the effect of increased drug dose on the efficacy and toxicity of the BEACOPP regimen with granulocyte colony-stimulating factor (G-CSF [Neupogen]) support in advanced-stage Hodgkins disease. Patients between 15 and 65 years old, either in stages IIB/IIIA with risk factors or in stages IIIB/IV, were eligible.
Eight courses of chemotherapy were followed by local irradiation of initial bulky and residual disease. From February 1993 to April 1998, 1,200 patients were randomized between standard COPP/ABVD (cyclophosphamide, Oncovin [vincristine], procarbazine(Drug information on procarbazine), and prednisone/Adriamycin [doxorubicin], bleomycin, vinblastine, and dacarbazine; arm A); baseline-dose BEACOPP (bleomycin, etoposide, Adriamycin, cyclophosphamide(Drug information on cyclophosphamide), Oncovin, procarbazine, and prednisone(Drug information on prednisone); arm B); and escalated-dose BEACOPP (arm C).
Baseline BEACOPP was approximately equivalent in dosage to COPP/ABVD but shortened to a 3-week course. Cyclophosphamide, etoposide, and doxorubicin(Drug information on doxorubicin) were escalated to 192%, 200%, and 140% of baseline, respectively, and G-CSF was administered in arm C from day 8 until leukocyte recovery.
This third interim analysis, in February 1998, was restricted to patients randomized before August 1996. Median observation time was 27 months. A total of 689 patients (91%) were evaluable.
Acute toxicity (neutropenia, thrombopenia, anemia, infection) with BEACOPP was increased but manageable; toxic deaths were no more frequent than with COPP/ABVD.
CONCLUSION: We conclude that moderate dose escalation is feasible and increases efficacy. Leukemogenicity must be monitored.