title: Comparison of chemotherapy including escalated BEACOPP versus chemotherapy including ABVD for patients with early unfavourable or advanced stage Hodgkin lymphoma.
abstract: BACKGROUND
  There are two different international standards for the treatment of early unfavourable and advanced stage Hodgkin lymphoma (HL): chemotherapy with escalated BEACOPP (bleomycin/etoposide/doxorubicin/cyclophosphamide/vincristine/procarbazine/prednisone) regimen and chemotherapy with ABVD (doxorubicin/bleomycin/vinblastine/dacarbazine) regimen.
  
  
  OBJECTIVE
  To provide an evidence-based answer regarding the advantages and disadvantages of chemotherapy including escalated BEACOPP compared to chemotherapy including ABVD.
  
  
  METHODS
  We searched for randomised controlled trials in MEDLINE, CENTRAL and conference proceedings (January 1985 to November 2010) and EMBASE (1985 to November 2008).
  
  
  METHODS
  We included randomised controlled trials examining chemotherapy including at least two cycles of escalated BEACOPP regimens compared to chemotherapy including at least four cycles of ABVD regimens as first-line treatment for patients with early unfavourable stage or advanced stage HL.
  
  
  METHODS
  Effect measures used were hazard ratios (HR) for overall survival (OS), progression-free survival (PFS) and freedom from first progression. Relative risks were used to analyse complete response rate, treatment-related mortality and adverse events. Two independent review authors extracted data and assessed quality of trials.
  
  
  RESULTS
  A total of 790 records were screened. Five eligible trials (four published, one ongoing), were identified. These trials included only adult patients (16 to 60 years of age). Four trials with 2868 patients were included in the meta-analyses: the HD9 and HD14 trials from Germany, the HD2000 and GSM-HD trials from Italy. All trials reported results for PFS and OS. PFS was statistically significantly longer for escalated BEACOPP: HR was 0.53 (95% confidence interval (CI) 0.44 to 0.64, I(2) = 0%). There was no statistically significant difference in OS between the comparators: HR was 0.80 (95% CI 0.59 to 1.09, I(2) = 0%). Three trials reported adverse events: the escalated BEACOPP regimens caused statistically significantly more haematological toxicities WHO grade III or IV (anaemia P < 0.00001, neutropenia P = 0.007, thrombocytopenia P < 0.00001), infections (P < 0.00001)) and occurrence of myeloid dysplastic syndrome (MDS) or acute myeloid leukemia (AML) (P = 0.05). There were no differences between both regimens for secondary malignancies, treatment-related mortality or infertility.
  
  
  CONCLUSIONS
  This meta-analysis showed that adult patients between 16 and 60 years of age with early unfavourable or advanced stage HL benefited from chemotherapy including escalated BEACOPP regarding PFS, but there was no significant difference in OS. Longer follow-up and the inclusion of the EORTC 20012 trial will lead to a more definitive answer with respect to OS.
authors.affiliation: Cochrane Haematological Malignancies Group, Department I of Internal Medicine, University Hospital of Cologne, Kerpener Str. 62, Cologne, Germany, 50924.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Bauer
authors.forename: Nicole
authors.initials: N
authors.lastname: Skoetz
authors.forename: Ina
authors.initials: I
authors.lastname: Monsef
authors.forename: Andreas
authors.initials: A
authors.lastname: Engert
authors.forename: Corinne
authors.initials: C
authors.lastname: Brillant
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D001761:Bleomycin / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage; D003606:Dacarbazine / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D006689:Hodgkin Disease / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage; D011344:Procarbazine / Q000008:administration & dosage; D016032:Randomized Controlled Trials as Topic; D014747:Vinblastine / Q000008:administration & dosage; D014750:Vincristine / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D001761:Bleomycin; D011344:Procarbazine; D014750:Vincristine; D014747:Vinblastine; D005047:Etoposide; D003606:Dacarbazine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone