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Blood, 15 November 2006, Vol. 108, No. 10, pp. 3262-3270. Prepublished online as a Blood First Edition Paper on July 20, 2006; DOI 10.1182/blood-2006-04-015560. This Article Full Text (PDF) All Versions of this Article: blood-2006-04-015560v1 108/10/3262    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Knapper, S. Articles by Small, D. Search for Related Content PubMed PubMed Citation Articles by Knapper, S. Articles by Small, D. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 13, 2006 Accepted June 28, 2006 A phase 2 trial of the FLT3 inhibitor lestaurtinib (CEP701) as first line treatment for older patients with acute myeloid leukemia not considered fit for intensive chemotherapy Steven Knapper, Alan K Burnett*, Tim Littlewood, W J Kell, Sam Agrawal, Raj Chopra, Richard Clark, Mark J Levis, and Donald Small Cardiff University, School of Medicine, Cardiff UK John Radcliffe Hospital Royal London Hospital, London UK Christie Hospital, Manchester, UK Royal Liverpool Hospital, UK Kimmel Cancer Center at Johns Hopkins Johns Hopkins University School of Medicine * Corresponding author; email: burnettak{at}cardiff.ac.uk. Activating mutations of FMS-like tyrosine kinase 3 (FLT3) are present in approximately one-third of cases of acute myeloid leukemia (AML) and are associated with adverse prognosis. The important role played by FLT3 in the survival and proliferation of blasts, and its overexpression in most AML patients make FLT3 an attractive therapeutic target. We undertook a phase 2 trial of the FLT3-selective tyrosine kinase inhibitor lestaurtinib (CEP701) used as monotherapy in untreated older AML patients not considered fit for intensive chemotherapy, irrespective of FLT3 mutation status. Lestaurtinib was administered orally for 8 weeks, initially at a dose of 60mg twice daily, escalating to 80mg twice daily, and was generally well tolerated. Clinical activity, manifest as transient reductions in bone marrow and peripheral blood blasts or longer periods of transfusion independence, was seen in 3 of 5 cases with mutated FLT3 (60%) and 5 of 22 evaluable wild type FLT3 patients (23%). Laboratory data demonstrated that clinical responses occurred where the presence of sustained FLT3-inhibitory drug levels were combined with in vitro cytotoxic sensitivity of blasts to lestaurtinib. Further evaluation of this compound, in combination with cytotoxic chemotherapy or other targeted agents, is warranted in both FLT3 mutant and wild type patients. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Older AML patients: fit for what? Richard M. Stone Blood 2006 108: 3232-3233. [Full Text] [PDF] This article has been cited by other articles: P. P. Zarrinkar, R. N. Gunawardane, M. D. Cramer, M. F. Gardner, D. Brigham, B. Belli, M. W. Karaman, K. W. Pratz, G. Pallares, Q. Chao, et al. AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML) Blood, October 1, 2009; 114(14): 2984 - 2992. [Abstract] [Full Text] [PDF] Y. Shiotsu, H. Kiyoi, Y. Ishikawa, R. 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