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Patients with acute myeloid leukemia and an activating mutation in FLT3 respond to a small-molecule FLT3 tyrosine kinase inhibitor, PKC412.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Stone, Richard M. Deangelo, Daniel J. Klimek, Virginia M. Galinsky, Ilene Estey, Eli Nimer, Stephen Grandin, Wilson Lebwohl, David Edward Wang, Yanfeng Cohen, Pamela Fox, Edward Alan Neuberg, Donna S. Clark, Jennifer Gilliland, Dwight Gary Griffin, James D. |
| Copyright Year | 2005 |
| Abstract | Leukemic cells from 30% of patients with acute myeloid leukemia (AML) have an activating mutation in the FLT3 (fms-like tyrosine kinase) gene, which represents a target for drug therapy. We treated 20 patients, each with mutant FLT3 relapsed/refractory AML or high-grade myelodysplastic syndrome and not believed to be candidates for chemotherapy, with an FLT3 tyrosine kinase inhibitor, PKC412 (N-benzoylstaurosporine), at a dose of 75 mg 3 times daily by mouth. The drug was generally well tolerated, although 2 patients developed fatal pulmonary events of unclear etiology. The peripheral blast count decreased by 50% in 14 patients (70%). Seven patients (35%) experienced a greater than 2-log reduction in peripheral blast count for at least 4 weeks (median response duration, 13 weeks; range, 9-47 weeks); PKC412 reduced bone marrow blast counts by 50% in 6 patients (2 of these to < 5%). FLT3 autophosphorylation was inhibited in most of the Corresponding patients, indicating in vivo target inhibition at the dose schedule used in this study. PKC412 is an oral tyrosine kinase inhibitor with clinical activity in patients with AML whose blasts have an activating mutation of FLT3, suggesting potential use in combination with active agents, such as chemotherapy. |
| Starting Page | 54 |
| Ending Page | 60 |
| Page Count | 7 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://bloodjournal.hematologylibrary.org/content/105/1/54.full.pdf |
| Alternate Webpage(s) | http://www.bloodjournal.org/content/bloodjournal/105/1/54.full.pdf?sso-checked=true |
| PubMed reference number | 15345597v1 |
| Volume Number | 105 |
| Issue Number | 1 |
| Journal | Blood |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Blast count procedure Bone Marrow FLT3 wt Allele Leukemia, Myelocytic, Acute MYELODYSPLASTIC SYNDROME Mutation Myeloid Leukemia Oral region PKC412 Patients Peripheral Vascular Diseases Protein Tyrosine Kinase Protein-tyrosine kinase inhibitor Vascular Endothelial Growth Factor Receptor-1 midostaurin |
| Content Type | Text |
| Resource Type | Article |
