title: Adaptive randomized study of idarubicin and cytarabine alone or with interleukin-11 as induction therapy in patients aged 50 or above with acute myeloid leukemia or high-risk myelodysplastic syndromes.
abstract: A higher complete remission (CR) rate was observed in patients with acute myeloid leukemia (AML) who, on a prior randomized study of induction therapy, received gemtuzumab ozogamicin (GO) plus interleukin-11 (IL-11) rather than GO alone. An adaptive randomized phase III study of the addition of IL-11 to idarubicin and cytarabine (IA) induction in 100 patients >/=50 years of age with AML or high-risk myelodysplastic syndrome (MDS) was conducted. Median patient age was 67 years (range 50-82). Twenty-four of the 45 (53%) patients randomized to IA plus IL-11 achieved CR. Eight (33%) subsequently relapsed, 4 (17%) died in CR; median time to treatment failure (TTF) was 37 weeks. Twenty-nine of the 55 (53%) patients treated without IL-11 achieved CR. Eight (28%) subsequently relapsed, 2 (7%) died in CR; median TTF was 46 weeks. Median overall survivals were 21 and 59 weeks for the IA plus IL-11 and IA cohorts, respectively (p=0.271, log rank test; 0.435, Gehan-Breslow test). Ten episodes of the following grade 3 or 4 cardiopulmonary toxicities were observed in patients receiving IA plus IL-11, 12 such episodes in those receiving IA alone: atrial fibrillation, pleural effusions, myocardial infarction, bradycardia or hypotension. Two patients in each arm experienced grade 3 peripheral edema. There was no significant difference in incidence of any grade 3 or 4 adverse event, including thrombocytopenia, between treatment arms. There was no significant impact on CR rates, TTF, survival, or toxicity of adding an IL-11 regimen to IA induction in patients >/=50 years of age with AML.
authors.affiliation: The University of Texas, M.D. Anderson Cancer Center, Department of Leukemia, Box 428, 1515 Holcombe Boulevard, Houston, TX 77030-4009, USA. fgiles@mdanderson.org
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Giles
authors.forename: Hagop M
authors.initials: HM
authors.lastname: Kantarjian
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Cortes
authors.forename: Stephan
authors.initials: S
authors.lastname: Faderl
authors.forename: Srdan
authors.initials: S
authors.lastname: Verstovsek
authors.forename: Deborah
authors.initials: D
authors.lastname: Thomas
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Manero
authors.forename: William
authors.initials: W
authors.lastname: Wierda
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ferrajoli
authors.forename: Stephen
authors.initials: S
authors.lastname: Kornblau
authors.forename: Gloria N
authors.initials: GN
authors.lastname: Mattiuzzi
authors.forename: Apostolia M
authors.initials: AM
authors.lastname: Tsimberidou
authors.forename: Maher
authors.initials: M
authors.lastname: Albitar
authors.forename: Susan M
authors.initials: SM
authors.lastname: O'Brien
authors.forename: Elihu
authors.initials: E
authors.lastname: Estey
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003561:Cytarabine / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage* / Q000009:adverse effects; D017370:Interleukin-11 / Q000008:administration & dosage* / Q000009:adverse effects; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy*; D012307:Risk Factors; D016019:Survival Analysis
chemical_list: D017370:Interleukin-11; D003561:Cytarabine; D015255:Idarubicin