The role of quizartinib in the treatment of acute myeloid leukemia.
BACKGROUND
Approximately one-third of the patients with acute myeloid leukemia (AML) harbor internal tandem duplication (ITD) in the gene encoding FMS-like tyrosine kinase 3 (FLT3-ITD), which is associated with poor prognosis. Over the course of the last decade, several FLT3 inhibitors have been developed. Nevertheless, the pharmacokinetic limitations of some of these compounds as well as their potency have limited their therapeutic efficacy. Quizartinib (AC220) is a second-generation FLT3 inhibitor that has shown promising activity in AML in Phase II clinical trials.


METHODS
The pharmacokinetic, mechanism of action and resistance as well as clinical studies of quizartinib in AML are reported here in detail.


CONCLUSIONS
Quizartinib is potent and selective FLT3 tyrosine kinase inhibitor with significant activity in both FLT3-mutant and wild-type AML. The quality and duration of achievable response thus far seen with this agent is suboptimal. Quizartinib in combination with chemotherapy might result in improved outcome and results of these trials are eagerly awaited. In addition, quizartinib in combination with other agents tackling the bone marrow microenvironment and FLT3 cooperative pathways may enhance response to quizartinib.
Fred Hutchinson Cancer Research Center , 1100 Fairview Ave N. D5-360, Seattle, WA 98109-1024 , USA +1 206 667 6045 ; +1 206 667-2324 ; fostrono@fhcrc.org.
Fabiana
F
Ostronoff
Elihu
E
Estey
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D052160:Benzothiazoles / Q000494:pharmacology / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics; D009154:Mutation; D010671:Phenylurea Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D051941:fms-Like Tyrosine Kinase 3 / Q000037:antagonists & inhibitors* / Q000235:genetics
D000970:Antineoplastic Agents; D052160:Benzothiazoles; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; C544967:quizartinib; D051941:fms-Like Tyrosine Kinase 3