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.

2.50
Hdl Handle:
http://hdl.handle.net/10541/72529
Title:
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.
Authors:
Knapper, Steven; Burnett, Alan K; Littlewood, Timothy; Kell, W Jonathan; Agrawal, Sam; Chopra, Rajesh; Clark, Richard E; Levis, Mark J; Small, Donald
Abstract:
Activating mutations of FMS-like tyrosine kinase 3 (FLT3) are present in approximately one third of patients with 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 patients with AML, 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 patients with AML not considered fit for intensive chemotherapy, irrespective of FLT3 mutation status. Lestaurtinib was administered orally for 8 weeks, initially at a dose of 60 mg twice daily, escalating to 80 mg 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 (60%) of 5 patients with mutated FLT3 and 5 (23%) of 22 evaluable wild-type FLT3 patients. 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.
Affiliation:
Department of Haematology, Cardiff University School of Medicine, Heath Park, Cardiff, CF14 4XW, United Kingdom.
Citation:
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. 2006, 108 (10):3262-70 Blood
Journal:
Blood
Issue Date:
15-Nov-2006
URI:
http://hdl.handle.net/10541/72529
DOI:
10.1182/blood-2006-04-015560
PubMed ID:
16857985
Type:
Article
Language:
en
ISSN:
0006-4971
Appears in Collections:
All Christie Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorKnapper, Steven-
dc.contributor.authorBurnett, Alan K-
dc.contributor.authorLittlewood, Timothy-
dc.contributor.authorKell, W Jonathan-
dc.contributor.authorAgrawal, Sam-
dc.contributor.authorChopra, Rajesh-
dc.contributor.authorClark, Richard E-
dc.contributor.authorLevis, Mark J-
dc.contributor.authorSmall, Donald-
dc.date.accessioned2009-07-06T08:57:25Z-
dc.date.available2009-07-06T08:57:25Z-
dc.date.issued2006-11-15-
dc.identifier.citationA 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. 2006, 108 (10):3262-70 Blooden
dc.identifier.issn0006-4971-
dc.identifier.pmid16857985-
dc.identifier.doi10.1182/blood-2006-04-015560-
dc.identifier.urihttp://hdl.handle.net/10541/72529-
dc.description.abstractActivating mutations of FMS-like tyrosine kinase 3 (FLT3) are present in approximately one third of patients with 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 patients with AML, 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 patients with AML not considered fit for intensive chemotherapy, irrespective of FLT3 mutation status. Lestaurtinib was administered orally for 8 weeks, initially at a dose of 60 mg twice daily, escalating to 80 mg 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 (60%) of 5 patients with mutated FLT3 and 5 (23%) of 22 evaluable wild-type FLT3 patients. 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.en
dc.language.isoenen
dc.subjectLeukaemiaen
dc.subject.meshAcute Disease-
dc.subject.meshAged-
dc.subject.meshAged, 80 and over-
dc.subject.meshAntineoplastic Agents-
dc.subject.meshBlood Cell Count-
dc.subject.meshCarbazoles-
dc.subject.meshFemale-
dc.subject.meshHumans-
dc.subject.meshIndoles-
dc.subject.meshLeukemia, Myeloid-
dc.subject.meshMale-
dc.subject.meshTreatment Outcome-
dc.subject.meshfms-Like Tyrosine Kinase 3-
dc.titleA 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.en
dc.typeArticleen
dc.contributor.departmentDepartment of Haematology, Cardiff University School of Medicine, Heath Park, Cardiff, CF14 4XW, United Kingdom.en
dc.identifier.journalBlooden

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