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.
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.
Giles
Francis J
FJ
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
Kantarjian
Hagop M
HM
Cortes
Jorge E
JE
Faderl
Stephan
S
Verstovsek
Srdan
S
Thomas
Deborah
D
Garcia-Manero
Guillermo
G
Wierda
William
W
Ferrajoli
Alessandra
A
Kornblau
Stephen
S
Mattiuzzi
Gloria N
GN
Tsimberidou
Apostolia M
AM
Albitar
Maher
M
O'Brien
Susan M
SM
Estey
Elihu
E
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
D017370:Interleukin-11; D003561:Cytarabine; D015255:Idarubicin