title: Two escalated followed by six standard BEACOPP in advanced-stage high-risk classical Hodgkin lymphoma: high cure rates but increased risk of aseptic osteonecrosis.
abstract: BACKGROUND
  From 1999, Norwegian guidelines recommend two escalated (esc) BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisolone) followed by six standard (s) BEACOPP for patients with advanced-stage classical Hodgkin lymphoma (HL) with an international prognostic score (IPS) ≥ 4. We evaluated retrospectively the experience with this recommendation at the Norwegian Radium Hospital, also including all IPS 3 patients treated with the same regimen.
  
  
  METHODS
  Forty-seven patients were treated between June 1999 and December 2008. IPS was 3 in 10 patients and ≥ 4 in 37.
  
  
  RESULTS
  Thirty-five patients received eight cycles of BEACOPP, 12 patients received one to six cycles only, mainly due to toxicity. Sixty percent of patients had dose reductions. With median follow-up of survivors of 89 months, 5-year progression-free and overall survival are 84% [95% confidence interval (CI) 73% to 95%] and 91% (95% CI 82% to 100%), respectively. Toxicity was considerable with grade 3 or more infections/febrile neutropenia in 66% of patients, including one death and three cases of Pneumocystis jiroveci pneumonia. Of note, 10 patients (21%) experienced symptomatic aseptic osteonecrosis, of whom 3 have had hip replacement surgery after treatment.
  
  
  CONCLUSIONS
  Two escBEACOPP plus six sBEACOPP is efficacious in advanced-stage high-risk HL. We document a high incidence of aseptic bone necrosis, possibly related to prednisolone.
authors.affiliation: Department of Oncology, Division of Surgery and Cancer Medicine. Electronic address: AFF@ous-hf.no.
authors.forename: A
authors.initials: A
authors.lastname: Fosså
authors.affiliation: Department of Oncology, Division of Surgery and Cancer Medicine.
authors.forename: I H
authors.initials: IH
authors.lastname: Fiskvik
authors.affiliation: Department of Oncology, Division of Surgery and Cancer Medicine.
authors.forename: A
authors.initials: A
authors.lastname: Kolstad
authors.affiliation: Department of Oncology, Division of Surgery and Cancer Medicine.
authors.forename: G F
authors.initials: GF
authors.lastname: Lauritzsen
authors.affiliation: Department of Oncology, Division of Surgery and Cancer Medicine.
authors.forename: E
authors.initials: E
authors.lastname: Aurlien
authors.affiliation: Department of Oncology, Division of Surgery and Cancer Medicine.
authors.forename: A K
authors.initials: AK
authors.lastname: Blystad
authors.affiliation: Department of Radiology.
authors.forename: K H
authors.initials: KH
authors.lastname: Hole
authors.affiliation: Department of Pathology, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, Norway.
authors.forename: I M
authors.initials: IM
authors.lastname: Ikonomou
authors.affiliation: Department of Oncology, Division of Surgery and Cancer Medicine.
authors.forename: H
authors.initials: H
authors.lastname: Holte
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects*; D001761:Bleomycin / Q000008:administration & dosage / Q000009:adverse effects; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D006689:Hodgkin Disease / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010020:Osteonecrosis / Q000139:chemically induced* / Q000175:diagnosis / Q000209:etiology / Q000401:mortality; D017410:Practice Guidelines as Topic / Q000592:standards; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D011344:Procarbazine / Q000008:administration & dosage / Q000009:adverse effects; D012189:Retrospective Studies; D012306:Risk; D016019:Survival Analysis; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects; D055815:Young Adult
chemical_list: D001761:Bleomycin; D011344:Procarbazine; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone