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A phase 1 study of SU11248 in the treatment of patients with refractory or resistant acute myeloid leukemia AML or not amenable to conventional therapy for the disease

by: W. Fiedler, H. Serve, H. Dohner, M. Schwittay, O. G. Ottmann, A. M. O'Farrell, C. L. Bello, R. Allred, W. C. Manning, J. M. Cherrington, S. G. Louie, W. Hong, N. M. Brega, G. Massimini, P. Scigalla, W. E. Berdel, and D. K. Hossfeld

In: Blood, Vol. 105, Nr. 3 (2005) , p. 986-993.

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URL:	PM:15459012

Fifteen patients with refractory AML were treated in a phase 1 study with SU11248, an oral kinase inhibitor of fms-like tyrosine kinase 3 Flt3, Kit, vascular endothelial growth factor VEGF, and platelet-derived growth factor PDGF receptors. Separate cohorts of patients received SU11248 for 4-week cycles followed by either a 2- or a 1-week rest period. At the starting dose level of 50 mg n = 13, no dose-limiting toxicities were observed. The most frequent grade 2 toxicities were edema, fatigue, and oral ulcerations. Two fatal bleedings possibly related to the disease, one from a concomitant lung cancer and one cerebral bleeding, were observed. At the 75 mg dose level n = 2, one case each of grade 4 fatigue, hypertension, and cardiac failure was observed, and this dose level was abandoned. All patients with FLT3 mutations n = 4 had morphologic or partial responses compared with 2 of 10 evaluable patients with wild-type FLT3. Responses, although longer in patients with mutated

BibTeX record

@article{Fiedler.2005,
  abstract = {Fifteen patients with refractory AML were treated in a phase 1 study with SU11248, an oral kinase inhibitor of fms-like tyrosine kinase 3 (Flt3), Kit, vascular endothelial growth factor (VEGF), and platelet-derived growth factor (PDGF) receptors. Separate cohorts of patients received SU11248 for 4-week cycles followed by either a 2- or a 1-week rest period. At the starting dose level of 50 mg (n = 13), no dose-limiting toxicities were observed. The most frequent grade 2 toxicities were edema, fatigue, and oral ulcerations. Two fatal bleedings possibly related to the disease, one from a concomitant lung cancer and one cerebral bleeding, were observed. At the 75 mg dose level (n = 2), one case each of grade 4 fatigue, hypertension, and cardiac failure was observed, and this dose level was abandoned. All patients with FLT3 mutations (n = 4) had morphologic or partial responses compared with 2 of 10 evaluable patients with wild-type FLT3. Responses, although longer in patients with mutated},
  added-at = {2010-02-05T11:28:39.000+0100},
  author = {Fiedler, W. and Serve, H. and Dohner, H. and Schwittay, M. and Ottmann, O. G. and O'Farrell, A. M. and Bello, C. L. and Allred, R. and Manning, W. C. and Cherrington, J. M. and Louie, S. G. and Hong, W. and Brega, N. M. and Massimini, G. and Scigalla, P. and Berdel, W. E. and Hossfeld, D. K.},
  biburl = {http://www.bibsonomy.org/bibtex/24927b533c5bbdadbcdd4591c087cdbf4/kanefendt},
  interhash = {ec4b51d42a997a7b44af704f725a3f6f},
  intrahash = {4927b533c5bbdadbcdd4591c087cdbf4},
  journal = {Blood},
  keywords = {& 3 Acute Aged Clearance Endothelial Factor Female Follow-Up Genotype Growth Human Humans Hypertension Indoles Kinase Kinases Leukemia Lung Male Metabolic Middle Mutation Myeloid Pharmacokinetics Platelet-Derived Protein-Tyrosine Proteins Proto-Oncogene Pyrroles Rate Receptor Receptors Research SU11248 Studies Tyrosine Vascular analysis antagonists cells drug fms-Like genetics inhibitors protein response therapeutic therapy toxicity use},
  number = 3,
  pages = {986-993},
  timestamp = {2010-02-05T11:28:39.000+0100},
  title = {A phase 1 study of SU11248 in the treatment of patients with refractory or resistant acute myeloid leukemia (AML) or not amenable to conventional therapy for the disease},
  url = {PM:15459012},
  volume = 105,
  year = 2005
}

Endnote record

%0 Journal Article
%1 Fiedler.2005
%A Fiedler, W.
%A Serve, H.
%A Dohner, H.
%A Schwittay, M.
%A Ottmann, O. G.
%A O'Farrell, A. M.
%A Bello, C. L.
%A Allred, R.
%A Manning, W. C.
%A Cherrington, J. M.
%A Louie, S. G.
%A Hong, W.
%A Brega, N. M.
%A Massimini, G.
%A Scigalla, P.
%A Berdel, W. E.
%A Hossfeld, D. K.
%D 2005
%J Blood
%K 
%N 3
%P 986-993
%T A phase 1 study of SU11248 in the treatment of patients with refractory or resistant acute myeloid leukemia (AML) or not amenable to conventional therapy for the disease
%U PM:15459012
%V 105
%X Fifteen patients with refractory AML were treated in a phase 1 study with SU11248, an oral kinase inhibitor of fms-like tyrosine kinase 3 (Flt3), Kit, vascular endothelial growth factor (VEGF), and platelet-derived growth factor (PDGF) receptors. Separate cohorts of patients received SU11248 for 4-week cycles followed by either a 2- or a 1-week rest period. At the starting dose level of 50 mg (n = 13), no dose-limiting toxicities were observed. The most frequent grade 2 toxicities were edema, fatigue, and oral ulcerations. Two fatal bleedings possibly related to the disease, one from a concomitant lung cancer and one cerebral bleeding, were observed. At the 75 mg dose level (n = 2), one case each of grade 4 fatigue, hypertension, and cardiac failure was observed, and this dose level was abandoned. All patients with FLT3 mutations (n = 4) had morphologic or partial responses compared with 2 of 10 evaluable patients with wild-type FLT3. Responses, although longer in patients with mutated

BibSonomy :: publication ::

A phase 1 study of SU11248 in the treatment of patients with refractory or resistant acute myeloid leukemia AML or not amenable to conventional therapy for the disease

Resources (URL, PDF, PS...)

Abstract

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Endnote record