title: Bortezomib added to daunorubicin and cytarabine during induction therapy and to intermediate-dose cytarabine for consolidation in patients with previously untreated acute myeloid leukemia age 60 to 75 years: CALGB (Alliance) study 10502.
abstract: OBJECTIVE
  The purpose of this study was to determine remission induction frequency when bortezomib was combined with daunorubicin and cytarabine in previously untreated older adults with acute myeloid leukemia (AML) and safety of bortezomib in combination with consolidation chemotherapy consisting of intermediate-dose cytarabine (Int-DAC).
  
  
  METHODS
  Ninety-five adults (age 60 to 75 years; median, 67 years) with previously untreated AML (including therapy-related and previous myelodysplastic syndrome) received bortezomib 1.3 mg/m(2) intravenously (IV) on days 1, 4, 8, and 11 with daunorubicin 60 mg/m(2) on days 1 through 3 and cytarabine 100 mg/m(2) by continuous IV infusion on days 1 through 7. Patients who achieved complete remission (CR) received up to two courses of consolidation chemotherapy with cytarabine 2 gm/m(2) on days 1 through 5 with bortezomib. Three cohorts with escalating dose levels of bortezomib were tested (0.7, 1.0, and 1.3 mg/m(2)). Dose-limiting toxicities were assessed during the first cycle of consolidation. The relationship between cell surface expression of CD74 and clinical outcome was assessed.
  
  
  RESULTS
  Frequency of CR was 65% (62 of 95), and 4% of patients (four of 95) achieved CR with incomplete platelet recovery (CRp). Eleven patients developed grade 3 sensory neuropathy. Bortezomib plus Int-DAC proved tolerable at the highest dose tested. Lower CD74 expression was associated with CR/CRp (P = .04) but not with disease-free or overall survival.
  
  
  CONCLUSIONS
  The addition of bortezomib to standard 3 + 7 daunorubicin and cytarabine induction chemotherapy for AML resulted in an encouraging remission rate. The maximum tested dose of bortezomib administered in combination with Int-DAC for remission consolidation was 1.3 mg/m(2) and proved tolerable. Further testing of this regimen is planned.
authors.affiliation: Massachusetts General Hospital Cancer Center, 100 Blossom St, Boston, MA 02114, USA. eattar@partners.org
authors.forename: Eyal C
authors.initials: EC
authors.lastname: Attar
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Johnson
authors.forename: Philip C
authors.initials: PC
authors.lastname: Amrein
authors.forename: Gerard
authors.initials: G
authors.lastname: Lozanski
authors.forename: Martha
authors.initials: M
authors.lastname: Wadleigh
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: DeAngelo
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Kolitz
authors.forename: Bayard L
authors.initials: BL
authors.lastname: Powell
authors.forename: Peter
authors.initials: P
authors.lastname: Voorhees
authors.forename: Eunice S
authors.initials: ES
authors.lastname: Wang
authors.forename: William
authors.initials: W
authors.lastname: Blum
authors.forename: Richard M
authors.initials: RM
authors.lastname: Stone
authors.forename: Guido
authors.initials: G
authors.lastname: Marcucci
authors.forename: Clara D
authors.initials: CD
authors.lastname: Bloomfield
authors.forename: Barry
authors.initials: B
authors.lastname: Moser
authors.forename: Richard A
authors.initials: RA
authors.lastname: Larson
mesh_terms: D000368:Aged; D000944:Antigens, Differentiation, B-Lymphocyte / Q000032:analysis; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001897:Boronic Acids / Q000008:administration & dosage / Q000009:adverse effects; D000069286:Bortezomib; D060830:Consolidation Chemotherapy / Q000379:methods*; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D003630:Daunorubicin / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D004357:Drug Synergism; D005260:Female; D005500:Follow-Up Studies; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D006801:Humans; D060828:Induction Chemotherapy / Q000379:methods*; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D017933:Peripheral Nervous System / Q000187:drug effects; D011719:Pyrazines / Q000008:administration & dosage / Q000009:adverse effects; D012074:Remission Induction; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000944:Antigens, Differentiation, B-Lymphocyte; D001897:Boronic Acids; D000949:Histocompatibility Antigens Class II; D011719:Pyrazines; C045084:invariant chain; D003561:Cytarabine; D000069286:Bortezomib; D003630:Daunorubicin