title: Phase IB study of the FLT3 kinase inhibitor midostaurin with chemotherapy in younger newly diagnosed adult patients with acute myeloid leukemia.
abstract: 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 50 mg twice daily for 14 days. A phase III prospective trial is ongoing (CALGB 10603, NCT00651261).
authors.affiliation: Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. rstone@partners.org
authors.forename: R M
authors.initials: RM
authors.lastname: Stone
authors.forename: T
authors.initials: T
authors.lastname: Fischer
authors.forename: R
authors.initials: R
authors.lastname: Paquette
authors.forename: G
authors.initials: G
authors.lastname: Schiller
authors.forename: C A
authors.initials: CA
authors.lastname: Schiffer
authors.forename: G
authors.initials: G
authors.lastname: Ehninger
authors.forename: J
authors.initials: J
authors.lastname: Cortes
authors.forename: H M
authors.initials: HM
authors.lastname: Kantarjian
authors.forename: D J
authors.initials: DJ
authors.lastname: DeAngelo
authors.forename: A
authors.initials: A
authors.lastname: Huntsman-Labed
authors.forename: C
authors.initials: C
authors.lastname: Dutreix
authors.forename: A
authors.initials: A
authors.lastname: del Corral
authors.forename: F
authors.initials: F
authors.lastname: Giles
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000201:enzymology / Q000401:mortality; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D012074:Remission Induction; D019311:Staurosporine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D015996:Survival Rate; D014018:Tissue Distribution; D016896:Treatment Outcome; D055815:Young Adult; D051941:fms-Like Tyrosine Kinase 3 / Q000037:antagonists & inhibitors* / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3; D019311:Staurosporine; C059539:midostaurin