Phase IB study of the FLT3 kinase inhibitor midostaurin with chemotherapy in younger newly diagnosed adult patients with acute myeloid leukemia

被引：225

作者：

Stone, R. M. ^{[1
]}

Fischer, T. ^{[2
]}

Paquette, R. ^{[3
]}

Schiller, G. ^{[3
]}

Schiffer, C. A. ^{[4
]}

Ehninger, G. ^{[5
]}

Cortes, J. ^{[6
]}

Kantarjian, H. M. ^{[6
]}

DeAngelo, D. J. ^{[1
]}

Huntsman-Labed, A. ^{[7
]}

Dutreix, C. ^{[7
]}

del Corral, A. ^{[8
]}

Giles, F. ^{[9
,10
]}

机构：

[1] Dana Farber Canc Inst, Boston, MA 02215 USA

[2] Otto von Guericke Univ, Med Ctr, Dept Hematol Oncol, Magdeburg, Germany

[3] UCLA Med Ctr, Los Angeles, CA USA

[4] Karmanos Canc Inst, Detroit, MI USA

[5] Tech Univ Dresden, D-01062 Dresden, Germany

[6] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA

[7] Novartis Pharma AG, Basel, Switzerland

[8] Novartis Oncol, E Hanover, NJ USA

[9] Natl Univ Ireland, HRB Clin Res Facil, Galway, Ireland

[10] Trinity Coll Dublin, Dublin, Ireland

来源：

LEUKEMIA | 2012年 / 26卷 / 09期

关键词：

FMS-like tyrosine kinase 3 receptor; acute myeloid leukemia; midostaurin; PKC412; newly diagnosed; ACUTE MYELOGENOUS LEUKEMIA; RISK MYELODYSPLASTIC SYNDROME; INTERNAL TANDEM DUPLICATIONS; POOR-PROGNOSIS; MUTANT FLT3; WILD-TYPE; GROUP-B; MUTATIONS; PKC412; CYTOGENETICS;

D O I：

10.1038/leu.2012.115

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

This phase 1b trial investigated several doses and schedules of midostaurin in combination with daunorubicin and cytarabine induction and high-dose cytarabine post-remission therapy in newly diagnosed patients with acute myeloid leukemia (AML). The discontinuation rate on the 50-mg twice-daily dose schedule was lower than 100 mg twice daily, and no grade 3/4 nausea or vomiting was seen. The complete remission rate for the midostaurin 50-mg twice-daily dose schedule was 80% (FMS-like tyrosine kinase 3 receptor (FLT3)-wild-type: 20 of 27 (74%), FLT3-mutant: 12 of 13 (92%)). Overall survival (OS) probabilities of patients with FLT3-mutant AML at 1 and 2 years (0.85 and 0.62, respectively) were similar to the FLT3-wild-type population (0.78 and 0.52, respectively). Midostaurin in combination with standard chemotherapy demonstrated high complete response and OS rates in newly diagnosed younger adults with AML, and was generally well tolerated at 50mg twice daily for 14 days. A phase III prospective trial is ongoing (CALGB 10603, NCT00651261).

引用

页码：2061 / 2068

页数：8

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