Acute hematologic toxicity and practicability of dose-intensified BEACOPP chemotherapy for advanced stage Hodgkin's disease

Background: Evidence is recently accumulating that the novel BEACOPP (bleom ycin (B), etoposide (E), adriamycin (A), cyclophosphamide (C), vincristine (O), procarbazine (P), prednisone (P)) chemotherapy is a highly effective t reatment for advanced stage Hodgkin's disease. Two dose variants of BEACOPP are currently tested in a phase III randomized multicenter trial of the GH SG. To enable more extensive testing of BEACOPP we characterized its practi cability regarding schedule adherence, acute hematotoxicity and need for su pportive treatment. Patients and methods: Data of 858 patients (6592 therapy cycles) from 184 p articipating institutions were evaluated. Planned total drug doses of the b aseline variant (arm 1) were 80, 2400, 200, 5200, 11.2, 5600 and 4480 mg/m( 2) for B, E, A, C, O, P and P, respectively. Compared to arm 1, the doses o f E, A and C in the dose-intensified variant (arm 2) were escalated by fact or 2.0, 1.4, 1.92, respectively, using G-CSF assistance. Stepwise dose redu ctions were specified in case of dose-limiting toxicities. Both variants ar e given in eight three-weekly courses. Results: Median dose adherence (dose actually given relative to planned arm 1 dose) in arm 1 was 1.0 for all drugs. Relative dose escalation of E, A, and C actually maintained in arm 2 was 1.83, 1.37 and 1.77 (medians), respe ctively, and 70% of patients maintained elevated dose levels throughout the entire treatment. Dose-limiting toxicities occurred in 25% of cycles in ar m 2, most frequently due to leukocytopenia and thrombocytopenia. Time cours es of leukocytes in arm 2 showed more severe but not more prolonged leukocy topenia compared with arm 1. WHO grades 3-4 infections were documented in 2 .1% (arm 1) and 3.1% (arm 2) of all cycles. Erythrocytes were transfused in 6% (arm 1) and 28% (arm 2), platelets in < 1% (arm 1) and 6% (arm 2) of al l cycles. Conclusions: Both BEACOPP schemes are practicable in a large multicenter se tting. Despite increased hematotoxicity, moderate dose escalation is safe f or the majority of the patients with G-CSF assistance and standard supporti ve treatment.