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Clinical potential of elacytarabine in patients with acute myeloid leukemia.
Ther Adv Hematol
December 2014
Duke University Medical Center - Medicine, 1149 North Pavilion Duke University Durham, NC 27710, USA.
Acute myeloid leukemia (AML) has been treated for over four decades with standard induction chemotherapy including seven days of cytosine arabinoside (cytarabine, ara-C) infusion. Cytarabine, while effective in killing leukemic cells, is subject to development of several resistance mechanisms rendering the drug ineffective in many patients. Elacytarabine, a lipophilic 5'-elaidic acid ester or nucleoside analogue of cytosine arabinoside, was created with the intent of overcoming resistance mechanisms including reduced expression of the human equilibrative nucleoside transporter 1 (hENT1) required for cytarabine entry into cells, as well as increased activity of cytidine deaminase (CDA) which breaks down the active metabolite of cytarabine, ara-CTP.
View Article and Find Full Text PDFNovel developments in the use of antimetabolites.
Nucleosides Nucleotides Nucleic Acids
February 2015
a Department of Medical Oncology , VU University Medical Center, 1081 HV , Amsterdam , The Netherlands.
Antimetabolites are the most widely used and most efficacious group of anticancer drugs. Antimetabolites are also the oldest rationally designed anticancer drugs, targeted against RNA and DNA, and can, therefore, be considered as the first generation of targeted drugs. Unfortunately, resistance often develops, leading to the design of new antimetabolites, which either have a novel mechanism of action, bypass resistance or in combination enhance the effect of other drugs, such as another antimetabolite, other DNA, or protein kinase targeted anticancer drugs.
View Article and Find Full Text PDFInternational randomized phase III study of elacytarabine versus investigator choice in patients with relapsed/refractory acute myeloid leukemia.
J Clin Oncol
June 2014
Gail J. Roboz, Weill Cornell Medical College and the New York Presbyterian Hospital; Todd Rosenblat, Columbia University Medical Center, New York, NY; Martha Arellano, Winship Cancer Institute at Emory University; Scott R. Solomon, The Blood and Marrow Transplant Group of Georgia, Atlanta, GA; Jessica K. Altman, Francis J. Giles, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL; Casey O'Connell, University of Southern California Norris Comprehensive Cancer Center and Hospital, Los Angeles, CA; Marco Gobbi, Azienda Ospedaliera Universitaria San Martino, University of Genoa, Genoa, Italy; Pau Montesinos, Hospital Universitario y Politécnico La Fé, Valencia, Spain; Arnaud Pigneux, Centre Hospitalier Universitaire de Bordeaux Hôpital Haut-Lévêque, Pessac; Norbert Vey, L'Institut Paoli-Calmettes, Marseilles, France; Robert Hills, Cardiff University School of Medicine, Cardiff, United Kingdom; Tove Flem Jacobsen, Athos Gianella-Borradori, Øivind Foss, and Sylvia Vetrhus, Clavis Pharma ASA, Oslo, Norway.
Purpose: Most patients with acute myeloid leukemia (AML) eventually experience relapse. Relapsed/refractory AML has a dismal prognosis and currently available treatment options are generally ineffective. The objective of this large, international, randomized clinical trial was to investigate the efficacy of elacytarabine, a novel elaidic acid ester of cytarabine, versus the investigator's choice of one of seven commonly used AML salvage regimens, including high-dose cytarabine, multiagent chemotherapy, hypomethylating agents, hydroxyurea, and supportive care.
View Article and Find Full Text PDFElacytarabine: lipid vector technology under investigation in acute myeloid leukemia.
Expert Rev Hematol
February 2013
HRB Clinical Research Facility, National University of Ireland Galway, Ireland.
Cytosine arabinoside (cytarabine or Ara-C) has been one of the cornerstones of treatment of acute myeloid leukemia since its approval in 1969. Standard induction therapy worldwide for all patients deemed fit for treatment (excluding those with acute promyelocytic leukemia) remains unchanged for over 40 years and consists of Ara-C administered by continuous infusion in combination with a topoisomerase II inhibitor (e.g.
View Article and Find Full Text PDFElacytarabine has single-agent activity in patients with advanced acute myeloid leukaemia.
Br J Haematol
September 2012
Department of Leukemia, University of Texas, MD Anderson Cancer Center, Houston, TX 77230, USA.
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.
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