Phase II trial of vorinostat with idarubicin and cytarabine for patients with newly diagnosed acute myelogenous leukemia or myelodysplastic syndrome

Guillermo Garcia-Manero, Francesco Paolo Tambaro, Nebiyou B. Bekele, Hui Yang, Farhad Ravandi, Elias Jabbour, Gautam Borthakur, Tapan M. Kadia, Marina Y. Konopleva, Stefan Faderl, Jorge E. Cortes, Mark Brandt, Yumin Hu, Deborah McCue, Willie Mae Newsome, Sherry R. Pierce, Marcos De Lima, Hagop M. Kantarjian

Research output: Contribution to journalArticle

110 Scopus citations


Purpose: 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). Patients and 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 x 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. Conclusion: The combination of vorinostat with idarubicin and cytarabine is safe and active in AML.

Original languageEnglish (US)
Pages (from-to)2204-2210
Number of pages7
JournalJournal of Clinical Oncology
Issue number18
Publication statusPublished - Jun 20 2012
Externally publishedYes


ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this