title: Phase II trial of subcutaneous recombinant human interleukin 11 with subcutaneous recombinant human granulocyte-macrophage colony stimulating factor in patients with acute myeloid leukemia (AML) receiving high-dose cytarabine during induction: ECOG 3997.
abstract: Randomized trials of substituting high-dose cytarabine (HiDAC) for standard dose cytarabine (SDAC) during induction therapy for newly diagnosed AML have not demonstrated an improvement in the complete remission (CR) rate. Phase II trials of the scheduled administration of HiDAC after SDAC suggest an improved outcome. The hematological complications of intensification are considerable. GM-CSF after chemotherapy improved the survival of older patients in a randomized trial. Recombinant human interleukin 11, a thrombopoietic cytokine, reduced the incidence of chemotherapy-induced thrombocytopenia in patients with solid tumors. Therefore, 34 patients were treated, with newly diagnosed AML less than 56 years of age, with daunorubicin 45 mg/m2 on days 1-3, cytarabine 100mg/m2 days 1-7 and cytarabine 2g/m2 for 12 h on days 8-10 (7+3+3). rhIL-11 (50 microg/kg/day,) and GM-CSF (250 microg/kg/day) were administered subcutaneously from day 11 until recovery. The complete remission rate was 59% (90% C.I. 43-73%). The median time to recovery of neutrophils to >500 and platelets to > or =20,000 microl(-1) was 27 days (95% C.I. 27-30 days) and 25 days (95% C.I. 24-29 days), respectively. The trial does not confirm the high CR rate observed in phase II trials, despite optimal supportive care.
authors.affiliation: Indiana University Medical Center, Indianapolis, IN, United States. lcripe@iupui.edu
authors.forename: Larry D
authors.initials: LD
authors.lastname: Cripe
authors.forename: Kevin
authors.initials: K
authors.lastname: Rader
authors.forename: Martin S
authors.initials: MS
authors.lastname: Tallman
authors.forename: Michael S
authors.initials: MS
authors.lastname: Gordon
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Paietta
authors.forename: John
authors.initials: J
authors.lastname: Bennett
authors.forename: Donna
authors.initials: D
authors.lastname: Neuberg
authors.forename: Mark R
authors.initials: MR
authors.lastname: Litzow
authors.forename: Timothy E
authors.initials: TE
authors.lastname: O'brien
authors.forename: Jacob M
authors.initials: JM
authors.lastname: Rowe
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003561:Cytarabine / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage*; D006801:Humans; D007279:Injections, Subcutaneous; D017370:Interleukin-11 / Q000008:administration & dosage*; D007951:Leukemia, Myeloid / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage; D012074:Remission Induction; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: C508611:IL11 protein, human; D017370:Interleukin-11; D011994:Recombinant Proteins; D003561:Cytarabine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor