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dc.contributor.authorO'Brien, Sen_GB
dc.contributor.authorRizzieri, Den_GB
dc.contributor.authorVey, Nen_GB
dc.contributor.authorRavandi, Fen_GB
dc.contributor.authorKrug, Uen_GB
dc.contributor.authorSekeres, Men_GB
dc.contributor.authorDennis, Michaelen_GB
dc.contributor.authorVenditti, Aen_GB
dc.contributor.authorBerry, Den_GB
dc.contributor.authorJacobsen, Ten_GB
dc.contributor.authorStaudacher, Ken_GB
dc.contributor.authorBergeland, Ten_GB
dc.contributor.authorGiles, Fen_GB
dc.date.accessioned2012-12-05T16:34:57Z
dc.date.available2012-12-05T16:34:57Z
dc.date.issued2012-09
dc.identifier.citationElacytarabine has single-agent activity in patients with advanced acute myeloid leukaemia. 2012, 158 (5):581-8 Br J Haematolen_GB
dc.identifier.issn1365-2141
dc.identifier.pmid22702906
dc.identifier.doi10.1111/j.1365-2141.2012.09186.x
dc.identifier.urihttp://hdl.handle.net/10541/254622
dc.description.abstractElacytarabine is a novel cytotoxic nucleoside analogue, independent of nucleoside transporters (e.g. human Equilibrative Nucleoside Transporter 1 [hENT1]) for cell uptake, and mechanisms of action similar to those of cytarabine. This Phase II study assessed the efficacy and safety of elacytarabine in patients with advanced stage acute myeloid leukaemia (AML). Patients received 2000 mg/m(2) per d continuously i.v. during days 1-5 every 3 weeks. Patients were matched by six risk factors with historical controls; remission rate (assessed after 1 or 2 cycles) and 6-month survival were compared. Sixty-one patients, median age 58 years, were enrolled; 52% had five or six risk factors. The remission rate was 18% (95% confidence interval: 9-30%) vs. 4% in controls (P < 0·0001), 6-month survival rate was 43%, median overall survival was 5·3 months (vs. 1·5 months); 10 patients (16%) were referred for stem cell transplantation after treatment. Side effects were predictable and manageable. The most common grade 3/4 non-haematological adverse events were febrile neutropenia, hypokalemia, fatigue, hyponatraemia, dyspnoea and pyrexia. Thirty-day all-cause mortality, after start of treatment, was 13% vs. 25% in controls. Elacytarabine has monotherapy activity in patients with advanced AML. This study provides proof-of-concept that lipid esterification of nucleoside analogues is clinically relevant.
dc.language.isoenen
dc.rightsArchived with thanks to British journal of haematologyen_GB
dc.subject.meshAdult
dc.subject.meshAged
dc.subject.meshAged, 80 and over
dc.subject.meshAntimetabolites, Antineoplastic
dc.subject.meshCytarabine
dc.subject.meshFemale
dc.subject.meshHumans
dc.subject.meshInfusions, Intravenous
dc.subject.meshLeukemia, Myeloid, Acute
dc.subject.meshMale
dc.subject.meshMiddle Aged
dc.subject.meshReferral and Consultation
dc.subject.meshRemission Induction
dc.subject.meshRisk Factors
dc.subject.meshStem Cell Transplantation
dc.subject.meshSurvival Rate
dc.subject.meshTreatment Outcome
dc.titleElacytarabine has single-agent activity in patients with advanced acute myeloid leukaemia.en
dc.typeArticleen
dc.contributor.departmentDepartment of Leukemia, University of Texas, MD Anderson Cancer Center, Houston, TX 77230, USA.en_GB
dc.identifier.journalBritish Journal of Haematologyen_GB
html.description.abstractElacytarabine is a novel cytotoxic nucleoside analogue, independent of nucleoside transporters (e.g. human Equilibrative Nucleoside Transporter 1 [hENT1]) for cell uptake, and mechanisms of action similar to those of cytarabine. This Phase II study assessed the efficacy and safety of elacytarabine in patients with advanced stage acute myeloid leukaemia (AML). Patients received 2000 mg/m(2) per d continuously i.v. during days 1-5 every 3 weeks. Patients were matched by six risk factors with historical controls; remission rate (assessed after 1 or 2 cycles) and 6-month survival were compared. Sixty-one patients, median age 58 years, were enrolled; 52% had five or six risk factors. The remission rate was 18% (95% confidence interval: 9-30%) vs. 4% in controls (P < 0·0001), 6-month survival rate was 43%, median overall survival was 5·3 months (vs. 1·5 months); 10 patients (16%) were referred for stem cell transplantation after treatment. Side effects were predictable and manageable. The most common grade 3/4 non-haematological adverse events were febrile neutropenia, hypokalemia, fatigue, hyponatraemia, dyspnoea and pyrexia. Thirty-day all-cause mortality, after start of treatment, was 13% vs. 25% in controls. Elacytarabine has monotherapy activity in patients with advanced AML. This study provides proof-of-concept that lipid esterification of nucleoside analogues is clinically relevant.


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