Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/12033
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dc.contributor.authorTan, Pen
dc.contributor.authorWei, Aen
dc.contributor.authorMithraprabhu, Sen
dc.contributor.authorCummings, Nen
dc.contributor.authorLiu, H Ben
dc.contributor.authorPerugini, Men
dc.contributor.authorReed, Ken
dc.contributor.authorAvery, Sen
dc.contributor.authorPatil, Sen
dc.contributor.authorWalker, Pen
dc.contributor.authorMollee, Pen
dc.contributor.authorGrigg, Andrew Pen
dc.contributor.authorD'Andrea, Ren
dc.contributor.authorDear, Aen
dc.contributor.authorSpencer, Aen
dc.date.accessioned2015-05-16T01:40:38Z
dc.date.available2015-05-16T01:40:38Z
dc.date.issued2014-01-10en
dc.identifier.citationBlood Cancer Journal 2014; 4(): e170en
dc.identifier.govdoc24413064en
dc.identifier.otherPUBMEDen
dc.identifier.urihttp://ahro.austin.org.au/austinjspui/handle/1/12033en
dc.description.abstractTherapeutic options are limited for elderly patients with acute myeloid leukemia (AML). A phase Ib/II study was undertaken to evaluate the maximum-tolerated dose (MTD) and preliminary efficacy of the pan-histone deacetylase inhibitor panobinostat (LBH589) in combination with azacitidine in patients with AML or high-risk myelodysplastic syndrome (MDS) naïve to intensive chemotherapy. Thirty-nine patients (AML=29, MDS=10) received azacitidine 75 mg/m(2) subcutaneously (days 1-5) and oral panobinostat (starting on day 5, thrice weekly for seven doses) in 28-day cycles until toxicity or disease progression. Dose-limiting toxicities during the phase Ib stage were observed in 0/4 patients receiving 10 mg panobinostat, in 1/7 patients (fatigue) receiving 20 mg, in 1/6 patients (fatigue) receiving 30 mg and in 4/5 patients (fatigue, syncope, hyponatremia and somnolence) receiving 40 mg. In phase II, an additional 17 patients received panobinostat at a MTD of 30 mg. The overall response rate (ORR=CR+CRi+PR) in patients with AML was 31% (9/29) and that in patients with MDS was 50% (5/10). After a median follow-up of 13 months, the median overall survival was 8 and 16 months in patients with AML and MDS, respectively. Increased histone H3 and H4 acetylation was a useful early biomarker of clinical response. Combining panobinostat with azacitidine was tolerable and clinically active in high-risk MDS/AML patients, warranting further exploration.en
dc.language.isoenen
dc.titleDual epigenetic targeting with panobinostat and azacitidine in acute myeloid leukemia and high-risk myelodysplastic syndrome.en
dc.typeJournal Articleen
dc.identifier.journaltitleBlood cancer journalen
dc.identifier.affiliationAustralian Centre for Blood Diseases, Biotechnology Division, Eastern Clinical Research Unit, Monash University, Melbourne, Victoria, Australiaen
dc.identifier.affiliationDepartment of Clinical Haematology, Alfred Hospital, Australian Centre for Blood Diseases, Monash University, Melbourne, Victoria, Australiaen
dc.identifier.affiliationInstitute of Medical and Veterinary Science, Department of Haematology and Centre for Cancer Biology, Adelaide, South Australia, Australiaen
dc.identifier.affiliationDivision of Cancer Services, Princess Alexandra Hospital, Brisbane, Queensland, Australiaen
dc.identifier.affiliationDepartment of Haematology, Austin Hospital, Melbourne, Victoria, Australiaen
dc.identifier.doi10.1038/bcj.2013.68en
dc.description.pagese170en
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pubmed/24413064en
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