title: Sequential combination of gemtuzumab ozogamicin and standard chemotherapy in older patients with newly diagnosed acute myeloid leukemia: results of a randomized phase III trial by the EORTC and GIMEMA consortium (AML-17).
abstract: OBJECTIVE
  This randomized trial evaluated the efficacy and toxicity of sequential gemtuzumab ozogamicin (GO) and standard chemotherapy in older patients with newly diagnosed acute myeloid leukemia (AML).
  
  
  METHODS
  Patients (n = 472) age 61 to 75 years were randomly assigned to induction chemotherapy with mitoxantrone, cytarabine, and etoposide preceded, or not, by a course of GO (6 mg/m(2) on days 1 and 15). In remission, patients received two consolidation courses with or without GO (3 mg/m(2) on day 0). The primary end point was overall survival (OS).
  
  
  RESULTS
  The overall response rate was comparable between the two arms (GO, 45%; no GO, 49%), but induction and 60-day mortality rates were higher in the GO arm (17% v 12% and 22% v 18%, respectively). With median follow-up of 5.2 years, median OS was 7.1 months in the GO arm and 10 months in the no-GO arm (hazard ratio, 1.20; 95% CI, 0.99 to 1.45; P = .07). Other survival end points were similar in both arms. Grade 3 to 4 hematologic and liver toxicities were greater in the GO arm. Treatment with GO provided no benefit in any prognostic subgroup, with the possible exception of patients age < 70 years with secondary AML, but outcomes were significantly worse in the oldest age subgroup because of a higher risk of early mortality.
  
  
  CONCLUSIONS
  As used in this trial, the sequential combination of GO and standard chemotherapy provides no benefit for older patients with AML and is too toxic for those age ≥ 70 years.
authors.affiliation: Sergio Amadori and Adriano Venditti, Tor Vergata University Hospital; Paolo De Fabritiis, St Eugenio Hospital; Roberto Latagliata, University Sapienza; Paola Fazi and Marco Vignetti, Gruppo Italiano Malattie Ematologiche dell'Adulto, Roma; Franca Falzetti, University Hospital, Perugia; Domenico Magro, Pugliese Hospital, Catanzaro; Giorgina Specchia, University Hospital, Bari, Italy; Stefan Suciu and Matthias Karrasch, European Organisation for Research and Treatment of Cancer, Brussels; Dominik Selleslag, Algemeen Ziekenhuis St Jan, Brugge; Zwi Berneman, University Hospital, Antwerp, Belgium; Roberto Stasi, St George's Hospital, London, United Kingdom; Helmut R. Salih, University Hospital, Tubingen; Anthony D. Ho, University Hospital, Heidelberg; Michael Lübbert, Albert Ludwigs University, Freiburg, Germany; Petra Muus and Theo de Witte, Radboud University Medical Centre, Nijmegen; Constantijn J.M. Halkes and Roel Willemze, University Medical Center, Leiden, the Netherlands; Xavier Thomas, Edouard Herriot Hospital, Lyon; Jean-Pierre Marie, St. Antoine Hospital, Paris, France; and José E. Guimaraes, University Hospital, Porto, Portugal.
authors.forename: Sergio
authors.initials: S
authors.lastname: Amadori
authors.forename: Stefan
authors.initials: S
authors.lastname: Suciu
authors.forename: Roberto
authors.initials: R
authors.lastname: Stasi
authors.forename: Helmut R
authors.initials: HR
authors.lastname: Salih
authors.forename: Dominik
authors.initials: D
authors.lastname: Selleslag
authors.forename: Petra
authors.initials: P
authors.lastname: Muus
authors.forename: Paolo
authors.initials: P
authors.lastname: De Fabritiis
authors.forename: Adriano
authors.initials: A
authors.lastname: Venditti
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Ho
authors.forename: Michael
authors.initials: M
authors.lastname: Lübbert
authors.forename: Xavier
authors.initials: X
authors.lastname: Thomas
authors.forename: Roberto
authors.initials: R
authors.lastname: Latagliata
authors.forename: Constantijn J M
authors.initials: CJ
authors.lastname: Halkes
authors.forename: Franca
authors.initials: F
authors.lastname: Falzetti
authors.forename: Domenico
authors.initials: D
authors.lastname: Magro
authors.forename: José E
authors.initials: JE
authors.lastname: Guimaraes
authors.forename: Zwi
authors.initials: Z
authors.lastname: Berneman
authors.forename: Giorgina
authors.initials: G
authors.lastname: Specchia
authors.forename: Matthias
authors.initials: M
authors.lastname: Karrasch
authors.forename: Paola
authors.initials: P
authors.lastname: Fazi
authors.forename: Marco
authors.initials: M
authors.lastname: Vignetti
authors.forename: Roel
authors.initials: R
authors.lastname: Willemze
authors.forename: Theo
authors.initials: T
authors.lastname: de Witte
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Marie
mesh_terms: D000208:Acute Disease; D000368:Aged; D000617:Aminoglycosides / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D064147:Febrile Neutropenia / Q000139:chemically induced; D005260:Female; D005500:Follow-Up Studies; D000079982:Gemtuzumab; D006801:Humans; D060828:Induction Chemotherapy / Q000379:methods; D007239:Infections / Q000139:chemically induced; D007951:Leukemia, Myeloid / Q000175:diagnosis / Q000188:drug therapy*; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage / Q000009:adverse effects; D012074:Remission Induction; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000617:Aminoglycosides; D061067:Antibodies, Monoclonal, Humanized; D003561:Cytarabine; D005047:Etoposide; D000079982:Gemtuzumab; D008942:Mitoxantrone