title: Acute hematologic toxicity and practicability of dose-intensified BEACOPP chemotherapy for advanced stage Hodgkin's disease. German Hodgkin's Lymphoma Study Group (GHSG).
abstract: BACKGROUND
  Evidence is recently accumulating that the novel BEACOPP (bleomycin (B), etoposide (E), adriamycin (A), cyclophosphamide (C), vincristine (O), procarbazine (P), prednisone (P)) chemotherapy is a highly effective treatment for advanced stage Hodgkin's disease. Two dose variants of BEACOPP are currently tested in a phase III randomized multicenter trial of the GHSG. To enable more extensive testing of BEACOPP we characterized its practicability regarding schedule adherence, acute hematotoxicity and need for supportive treatment.
  
  
  METHODS
  Data of 858 patients (6592 therapy cycles) from 184 participating institutions were evaluated. Planned total drug doses of the baseline variant (arm 1) were 80, 2400, 200, 5200, 11.2, 5600 and 4480 mg/m2 for B, E, A, C, O, P and P, respectively. Compared to arm 1, the doses of E, A and C in the dose-intensified variant (arm 2) were escalated by factor 2.0, 1.4, 1.92, respectively, using G-CSF assistance. Stepwise dose reductions were specified in case of dose-limiting toxicities. Both variants are 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), respectively, and 70% of patients maintained elevated dose levels throughout the entire treatment. Dose-limiting toxicities occurred in 25% of cycles in arm 2, most frequently due to leukocytopenia and thrombocytopenia. Time courses of leukocytes in arm 2 showed more severe but not more prolonged leukocytopenia 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 61% (arm 1) and 28% (arm 2), platelets in < 1% (arm 1) and 6% (arm 2) of all cycles.
  
  
  CONCLUSIONS
  Both BEACOPP schemes are practicable in a large multicenter setting. Despite increased hematotoxicity, moderate dose escalation is safe for the majority of the patients with G-CSF assistance and standard supportive treatment.
authors.affiliation: Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Germany. engel@imise.uni-leipzig.de
authors.forename: C
authors.initials: C
authors.lastname: Engel
authors.forename: M
authors.initials: M
authors.lastname: Loeffler
authors.forename: S
authors.initials: S
authors.lastname: Schmitz
authors.forename: H
authors.initials: H
authors.lastname: Tesch
authors.forename: V
authors.initials: V
authors.lastname: Diehl
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001761:Bleomycin / Q000008:administration & dosage* / Q000009:adverse effects; D001792:Blood Platelets / Q000187:drug effects*; D001803:Blood Transfusion; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000009:adverse effects; D018450:Disease Progression; D004317:Doxorubicin / Q000008:administration & dosage* / Q000009:adverse effects; D005047:Etoposide / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006689:Hodgkin Disease / Q000188:drug therapy* / Q000532:radiotherapy; D006801:Humans; D007958:Leukocyte Count; D007962:Leukocytes / Q000187:drug effects*; D007970:Leukopenia / Q000139:chemically induced*; D008297:Male; D008875:Middle Aged; D010976:Platelet Count; D011241:Prednisone / Q000008:administration & dosage* / Q000009:adverse effects; D011344:Procarbazine / Q000008:administration & dosage* / Q000009:adverse effects; D016019:Survival Analysis; D013921:Thrombocytopenia / Q000139:chemically induced*; D013997:Time Factors; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D001761:Bleomycin; D011344:Procarbazine; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone