A phase I study of midostaurin and azacitidine in relapsed and elderly AML patients.
Clin Lymphoma Myeloma Leuk
; 15(7): 428-432.e2, 2015 Jul.
Article
em En
| MEDLINE
| ID: mdl-25776192
ABSTRACT
BACKGROUND:
Midostaurin is a novel, orally available Fms-like tyrosine kinase 3 (FLT3) tyrosine kinase inhibitor that induces cell cycle arrest and apoptosis of leukemic cells expressing mutant and wild type FLT3 receptors, and has shown potential synergism with cytotoxic chemotherapy. PATIENTS ANDMETHODS:
We conducted a phase I study of azacitidine (intravenous 75 mg/m(2) daily for 7 days) with escalating doses of oral midostaurin (25 mg twice per day [b.i.d.], 50 mg b.i.d., and 75 mg b.i.d.) on days 8 to 21 of a 28-day cycle in untreated acute myeloid leukemia (AML) in older patients and/or relapsed AML. Patients were eligible regardless of FLT3 mutation status. Trough blood samples for pharmacokinetics were obtained on days 8, 15, and 21 before midostaurin dosing.RESULTS:
Seventeen patients with a median age of 73 (range, 57-83) years were enrolled; 5 patients had previous conventional treatment and none of the patients had FLT3 mutations. Dose-limiting toxicities were not observed. Hospitalizations, primarily for infections, occurred in one-third of treatment cycles. Fourteen patients were evaluable for response 3 attained complete remission and 2 had hematologic improvement. Median (range) survival from enrollment was 6 (1 to ≥ 19) months. Three patients died within 60 days of enrollment (2 progressive disease, 1 non-dose-limiting toxicity, treatment-related). Pharmacokinetic data at 75 mg orally b.i.d. showed increased trough levels of midostaurin during cycle 2 compared with cycle 1 and persistent and increasing levels of its active metabolite, CGP52421.CONCLUSION:
The combination of sequential azacitidine and midostaurin is safe and tolerable with response rates comparable with azacitidine alone and should be studied further in FLT3 mutation-positive AML.Palavras-chave
Texto completo:
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Bases de dados:
MEDLINE
Assunto principal:
Azacitidina
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Leucemia Mieloide Aguda
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Estaurosporina
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Recidiva Local de Neoplasia
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Antimetabólitos Antineoplásicos
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Antineoplásicos
Tipo de estudo:
Clinical_trials
Limite:
Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Clin Lymphoma Myeloma Leuk
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2015
Tipo de documento:
Article