TY - JOUR
T1 - Phase II trial of vorinostat with idarubicin and cytarabine for patients with newly diagnosed acute myelogenous leukemia or myelodysplastic syndrome
AU - Garcia-Manero, Guillermo
AU - Tambaro, Francesco Paolo
AU - Bekele, Nebiyou B.
AU - Yang, Hui
AU - Ravandi, Farhad
AU - Jabbour, Elias
AU - Borthakur, Gautam
AU - Kadia, Tapan M.
AU - Konopleva, Marina Y.
AU - Faderl, Stefan
AU - Cortes, Jorge E.
AU - Brandt, Mark
AU - Hu, Yumin
AU - McCue, Deborah
AU - Newsome, Willie Mae
AU - Pierce, Sherry R.
AU - De Lima, Marcos
AU - Kantarjian, Hagop M.
PY - 2012/6/20
Y1 - 2012/6/20
N2 - 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.
AB - 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.
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U2 - 10.1200/JCO.2011.38.3265
DO - 10.1200/JCO.2011.38.3265
M3 - Article
C2 - 22585696
AN - SCOPUS:84864011031
SN - 0732-183X
VL - 30
SP - 2204
EP - 2210
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 18
ER -