Abstract
Outcome of patients with myelodysplastic syndrome after azacitidine failure is poor. In this population, we combined cytarabine (10-20mg/m²/day 14 days) with vorinostat (400mg/day) for escalating durations (7 days, 10 days and 14 days), and starting on day 1 (concomitant arm) or on day 14 (sequential arm) following a 3+3 phase I design. 40 patients were treated. Dose limiting toxicities were all seen in sequential arm. The overall response rate was 15% with 4 responses in concomitant arm (ORR=25%). We conclude that this combination is tolerable and concomitant administration might be less toxic and have better therapeutic effect (clinicaltrials.gov NCT00776503).
Keywords:
Azacitidine failure; Epigenetic; HDAC; Myelodysplasia.
Copyright © 2013 Elsevier Ltd. All rights reserved.
Publication types
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Clinical Trial, Phase I
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Clinical Trial, Phase II
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Multicenter Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Aged
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Aged, 80 and over
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Antineoplastic Combined Chemotherapy Protocols / adverse effects
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
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Azacitidine / administration & dosage
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Cytarabine / administration & dosage
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Cytarabine / adverse effects
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Dose-Response Relationship, Drug
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Drug Administration Schedule
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Drug Resistance, Neoplasm
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Female
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Humans
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Hydroxamic Acids / administration & dosage
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Hydroxamic Acids / adverse effects
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In Vitro Techniques
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Middle Aged
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Myelodysplastic Syndromes / drug therapy*
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Myelodysplastic Syndromes / pathology
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Nausea / chemically induced
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Neutropenia / chemically induced
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Recurrence
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Risk Factors
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Survival Analysis
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Thrombocytopenia / chemically induced
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Treatment Outcome
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Vomiting / chemically induced
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Vorinostat
Substances
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Hydroxamic Acids
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Cytarabine
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Vorinostat
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Azacitidine
Associated data
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ClinicalTrials.gov/NCT00776503