Dataset Information

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

ABSTRACT:

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 × 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.

SUBMITTER: Garcia-Manero G

PROVIDER: S-EPMC4879705 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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Publications

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

Garcia-Manero Guillermo G Tambaro Francesco Paolo FP Bekele Nebiyou B NB Yang Hui H Ravandi Farhad F Jabbour Elias E Borthakur Gautam G Kadia Tapan M TM Konopleva Marina Y MY Faderl Stefan S Cortes Jorge E JE Brandt Mark M Hu Yumin Y McCue Deborah D Newsome Willie Mae WM Pierce Sherry R SR de Lima Marcos M Kantarjian Hagop M HM

Journal of clinical oncology : official journal of the American Society of Clinical Oncology 20120514 18

<h4>Purpose</h4>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).<h4>Patients and methods</h4>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 ...[more]

PMID: 22585696

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Dataset Information

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

Purpose

Patients and methods

Results

Conclusion

Publications

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

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