title: Phase II trial of vorinostat with idarubicin and cytarabine for patients with newly diagnosed acute myelogenous leukemia or myelodysplastic syndrome.
abstract: OBJECTIVE
  To evaluate the safety and efficacy of the combination of the histone deacetylase inhibitor vorinostat with idarubicin and ara-C (cytarabine) in patients with acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS).
  
  
  METHODS
  Patients with previously untreated AML or higher-risk MDS age 15 to 65 years with appropriate organ function and no core-binding factor abnormality were candidates. Induction therapy was vorinostat 500 mg orally three times a day (days 1 to 3), idarubin 12 mg/m(2) intravenously (IV) daily × 3 (days 4 to 6), and cytarabine 1.5 g/m(2) IV as a continuous infusion daily for 3 or 4 days (days 4 to 7). Patients in remission could be treated with five cycles of consolidation therapy and up to 12 months of maintenance therapy with single-agent vorinostat. The study was designed to stop early if either excess toxicity or low probability of median event-free survival (EFS) of more than 28 weeks was likely.
  
  
  RESULTS
  After a three-patient run-in phase, 75 patients were treated. Median age was 52 years (range, 19 to 65 years), 29 patients (39%) were cytogenetically normal, and 11 (15%) had FLT-3 internal tandem duplication (ITD). No excess vorinostat-related toxicity was observed. Induction mortality was 4%. EFS was 47 weeks (range, 3 to 134 weeks), and overall survival was 82 weeks (range, 3 to 134 weeks). Overall response rate (ORR) was 85%, including 76% complete response (CR) and 9% in CR with incomplete platelet recovery. ORR was 93% in diploid patients and 100% in FLT-3 ITD patients. Levels of NRF2 and CYBB were associated with longer survival.
  
  
  CONCLUSIONS
  The combination of vorinostat with idarubicin and cytarabine is safe and active in AML.
authors.affiliation: Department of Leukemia, University of Texas, MD Anderson Cancer Center, 1515 Holcombe Blvd, Box 428, Houston, TX 77025, USA. ggarciam@mdanderson.org
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Manero
authors.forename: Francesco Paolo
authors.initials: FP
authors.lastname: Tambaro
authors.forename: Nebiyou B
authors.initials: NB
authors.lastname: Bekele
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
authors.forename: Farhad
authors.initials: F
authors.lastname: Ravandi
authors.forename: Elias
authors.initials: E
authors.lastname: Jabbour
authors.forename: Gautam
authors.initials: G
authors.lastname: Borthakur
authors.forename: Tapan M
authors.initials: TM
authors.lastname: Kadia
authors.forename: Marina Y
authors.initials: MY
authors.lastname: Konopleva
authors.forename: Stefan
authors.initials: S
authors.lastname: Faderl
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Cortes
authors.forename: Mark
authors.initials: M
authors.lastname: Brandt
authors.forename: Yumin
authors.initials: Y
authors.lastname: Hu
authors.forename: Deborah
authors.initials: D
authors.lastname: McCue
authors.forename: Willie Mae
authors.initials: WM
authors.lastname: Newsome
authors.forename: Sherry R
authors.initials: SR
authors.lastname: Pierce
authors.forename: Marcos
authors.initials: M
authors.lastname: de Lima
authors.forename: Hagop M
authors.initials: HM
authors.lastname: Kantarjian
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage*; D015255:Idarubicin / Q000008:administration & dosage*; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000401:mortality; D012008:Recurrence; D000077337:Vorinostat
chemical_list: D006877:Hydroxamic Acids; D000077337:Vorinostat; D015255:Idarubicin