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Elacytarabine has single-agent activity in patients with advanced acute myeloid leukaemia

O'Brien, Susan ; Rizzieri, David A. ; Vey, Norbert ; Ravandi, Farhad ; Krug, Utz O. ; Sekeres, Mikkael A. ; Dennis, Mike ; Venditti, Adriano ; Berry, Donald A. ; Jacobsen, Tove Flem ; Staudacher, Karin ; Bergeland, Trygve ; Giles, Francis J.

British journal of haematology, 2012-09, Vol.158 (5), p.581-588 [Periódico revisado por pares]

Oxford: Blackwell Publishing Ltd

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Título:
Elacytarabine has single-agent activity in patients with advanced acute myeloid leukaemia
Autor: O'Brien, Susan ; Rizzieri, David A. ; Vey, Norbert ; Ravandi, Farhad ; Krug, Utz O. ; Sekeres, Mikkael A. ; Dennis, Mike ; Venditti, Adriano ; Berry, Donald A. ; Jacobsen, Tove Flem ; Staudacher, Karin ; Bergeland, Trygve ; Giles, Francis J.
Assuntos: Adult ; Age ; Aged ; Aged, 80 and over ; Antimetabolites, Antineoplastic - administration & dosage ; Antimetabolites, Antineoplastic - adverse effects ; Biological and medical sciences ; Cell survival ; cytarabine ; Cytarabine - administration & dosage ; Cytarabine - adverse effects ; Cytarabine - analogs & derivatives ; Cytotoxicity ; Dyspnea ; elacytarabine ; Esterification ; Fatigue ; Female ; Fever ; Hematologic and hematopoietic diseases ; Humans ; Hypokalemia ; Infusions, Intravenous ; Leukemia, Myeloid, Acute - drug therapy ; Leukemia, Myeloid, Acute - mortality ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; lipid esterification ; Lipids ; Male ; Medical sciences ; Middle Aged ; Mortality ; Neutropenia ; nucleoside analogs ; nucleoside analogue ; nucleoside transporter ; Referral and Consultation ; Remission ; Remission Induction ; Respiration ; Risk Factors ; Side effects ; Stem Cell Transplantation ; Survival ; Survival Rate ; Treatment Outcome
É parte de: British journal of haematology, 2012-09, Vol.158 (5), p.581-588
Notas: istex:D069E91E880C795D90EB8B077F0A5C82D2BAA854
ArticleID:BJH9186
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ObjectType-Article-2
SourceType-Scholarly Journals-1
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Descrição: Summary Elacytarabine 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/m2 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.
Editor: Oxford: Blackwell Publishing Ltd
Idioma: Inglês

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Elacytarabine has single-agent activity in patients with advanced acute myeloid leukaemia

O'Brien, Susan ; Rizzieri, David A. ; Vey, Norbert ; Ravandi, Farhad ; Krug, Utz O. ; Sekeres, Mikkael A. ; Dennis, Mike ; Venditti, Adriano ; Berry, Donald A. ; Jacobsen, Tove Flem ; Staudacher, Karin ; Bergeland, Trygve ; Giles, Francis J.

Oxford: Blackwell Publishing Ltd

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