title: Dose-intensification in early unfavorable Hodgkin's lymphoma: final analysis of the German Hodgkin Study Group HD14 trial.
abstract: OBJECTIVE
  In patients with early unfavorable Hodgkin's lymphoma (HL), combined modality treatment with four cycles of ABVD (adriamycin, bleomycin, vinblastine, and dacarbazine) and 30 Gy involved-field radiotherapy (IFRT) results in long-term tumor control of approximately 80%. We aimed to improve these results using more intensive chemotherapy.
  
  
  METHODS
  Patients with newly diagnosed early unfavorable HL were randomly assigned to either four cycles of ABVD or an intensified treatment consisting of two cycles of escalated BEACOPP (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, and prednisone) followed by two cycles of ABVD (2 + 2). Chemotherapy was followed by 30 Gy IFRT in both arms. The primary end point was freedom from treatment failure (FFTF); secondary end points included progression-free survival (PFS) and treatment-related toxicity.
  
  
  RESULTS
  With a total of 1,528 qualified patients included, the 2 + 2 regimen demonstrated superior FFTF compared with four cycles of ABVD (P < .001; hazard ratio, 0.44; 95% CI, 0.30 to 0.66), with a difference of 7.2% at 5 years (95% CI, 3.8 to 10.5). The difference in 5-year PFS was 6.2% (95% CI, 3.0% to 9.5%). There was more acute toxicity associated with 2 + 2 than with ABVD, but there were no overall differences in treatment-related mortality or secondary malignancies.
  
  
  CONCLUSIONS
  Intensified chemotherapy with two cycles of BEACOPP escalated followed by two cycles of ABVD followed by IFRT significantly improves tumor control in patients with early unfavorable HL.
authors.affiliation: University of Cologne, Cologne, Germany.
authors.forename: Bastian
authors.initials: B
authors.lastname: von Tresckow
authors.forename: Annette
authors.initials: A
authors.lastname: Plütschow
authors.forename: Michael
authors.initials: M
authors.lastname: Fuchs
authors.forename: Beate
authors.initials: B
authors.lastname: Klimm
authors.forename: Jana
authors.initials: J
authors.lastname: Markova
authors.forename: Andreas
authors.initials: A
authors.lastname: Lohri
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Kral
authors.forename: Richard
authors.initials: R
authors.lastname: Greil
authors.forename: Max S
authors.initials: MS
authors.lastname: Topp
authors.forename: Julia
authors.initials: J
authors.lastname: Meissner
authors.forename: Josée M
authors.initials: JM
authors.lastname: Zijlstra
authors.forename: Martin
authors.initials: M
authors.lastname: Soekler
authors.forename: Harald
authors.initials: H
authors.lastname: Stein
authors.forename: Hans T
authors.initials: HT
authors.lastname: Eich
authors.forename: Rolf P
authors.initials: RP
authors.lastname: Mueller
authors.forename: Volker
authors.initials: V
authors.lastname: Diehl
authors.forename: Peter
authors.initials: P
authors.lastname: Borchmann
authors.forename: Andreas
authors.initials: A
authors.lastname: Engert
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001761:Bleomycin / Q000008:administration & dosage; D059248:Chemoradiotherapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D003606:Dacarbazine / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006689:Hodgkin Disease / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage; D011344:Procarbazine / Q000008:administration & dosage; D015996:Survival Rate; D016896:Treatment Outcome; 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