@article{c113fd12c3114d05ae764421472841ce,
title = "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",
abstract = "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.",
author = "Thomas Fischer and Stone, {Richard M.} and DeAngelo, {Daniel J.} and Ilene Galinsky and Elihu Estey and Carlo Lanza and Edward Fox and Gerhard Ehninger and Feldman, {Eric J.} and Schiller, {Gary J.} and Klimek, {Virginia M.} and Nimer, {Stephen D} and Gilliland, {D. Gary} and Catherine Dutreix and Alice Huntsman-Labed and Jodi Virkus and Giles, {Francis J.}",
year = "2010",
month = oct
day = "1",
doi = "10.1200/JCO.2010.28.9678",
language = "English",
volume = "28",
pages = "4339--4345",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "28",
}