| Phase IIB trial of oral Midostaurin (PKC412), the FMS-like tyrosine kinase 3 receptor (FLT3) and multi-targeted kinase inhibitor, in patients with acute myeloid leukemia and high-risk myelodysplastic syndrome with either wild-type or mutated FLT3. | |
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MedLine Citation:
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PMID: 20733134 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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PURPOSE: Mutations leading to constitutive activation of the FMS-like tyrosine kinase 3 receptor (FLT3) occur in blasts of 30% of patients with acute myeloid leukemia (AML). Midostaurin (PKC412; N-benzoylstaurosporin) is a multitargeted tyrosine kinase inhibitor, with demonstrated activity in patients with AML/myelodysplastic syndrome (MDS) with FLT3 mutations. PATIENTS AND METHODS: Ninety-five patients with AML or MDS with either wild-type (n = 60) or mutated (n = 35) FLT3 were randomly assigned to receive oral midostaurin at 50 or 100 mg twice daily. The drug was discontinued in the absence of response at 2 months, disease progression, or unacceptable toxicity. Response was defined as complete response, partial response (PR), hematologic improvement, or reduction in peripheral blood or bone marrow blasts by ≥ 50% (BR). RESULTS: The rate of BR for the population in whom efficacy could be assessed (n = 92) was 71% in patients with FLT3-mutant and 42% in patients with FLT3 wild-type. One PR occurred in a patient with FLT3-mutant receiving the 100-mg dose regimen. Both doses were well-tolerated; there were no differences in toxicity or response rate according to the dose of midostaurin. CONCLUSION: These results suggest that midostaurin has hematologic activity in both patients with FLT3-mutant and wild-type. The degree of clinical activity observed supports additional studies that combine midostaurin and other agents such as chemotherapy especially in FLT3-mutant AML. |
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Authors:
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Thomas Fischer; Richard M Stone; Daniel J Deangelo; Ilene Galinsky; Elihu Estey; Carlo Lanza; Edward Fox; Gerhard Ehninger; Eric J Feldman; Gary J Schiller; Virginia M Klimek; Stephen D Nimer; D Gary Gilliland; Catherine Dutreix; Alice Huntsman-Labed; Jodi Virkus; Francis J Giles |
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Publication Detail:
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Type: Clinical Trial, Phase II; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't Date: 2010-08-23 |
Journal Detail:
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Title: Journal of clinical oncology : official journal of the American Society of Clinical Oncology Volume: 28 ISSN: 1527-7755 ISO Abbreviation: J. Clin. Oncol. Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-09-30 Completed Date: 2010-11-02 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8309333 Medline TA: J Clin Oncol Country: United States |
Other Details:
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Languages: eng Pagination: 4339-45 Citation Subset: IM |
Affiliation:
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Dana-Farber Cancer Institute, 44 Binney St, Boston, MA 02115, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Administration, Oral Aged Antineoplastic Agents / administration & dosage, adverse effects, therapeutic use* Female Humans Leukemia, Myeloid, Acute / drug therapy*, enzymology, genetics* Male Mutation Myelodysplastic Syndromes / drug therapy*, enzymology, genetics* Receptor Protein-Tyrosine Kinases / genetics Staurosporine / administration & dosage, adverse effects, analogs & derivatives*, therapeutic use Treatment Outcome fms-Like Tyrosine Kinase 3 / genetics* |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/PKC412; 120685-11-2/4'-N-benzoylstaurosporine; 62996-74-1/Staurosporine; EC 2.7.10.1/Receptor Protein-Tyrosine Kinases; EC 2.7.10.1/fms-Like Tyrosine Kinase 3 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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