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Drugs Fut 2017, 42(5): 265
ISSN 0377-8282
Copyright 2017 Clarivate Analytics
CCC: 0377-8282
DOI: 10.1358/dof.2017.042.05.2618154
Glasdegib. Hedgehog signaling inhibitor, Treatment of myelodysplastic syndrome, Treatment of chronic myelomonocytic leukemia, Treatment of acute myeloid leukemia, Treatment of myelofibrosis
Gras, J.
Acute myeloid leukemia (AML) is the most common acute leukemia affecting adults. The median age at diagnosis is 67 years, and the 5-year relative survival is a dismal 26%. Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic disorders with an increased likelihood of progression to AML. Glasdegib (PF-04449913) selectively and potently inhibits Smoothened activation, thus blocking the hedgehog pathway. In a phase II clinical trial, glasdegib orally at 100 mg daily combined with low-dose cytarabine significantly improved complete remission and overall survival in comparison with low-dose cytarabine alone in AML and high-risk MDS patients. Glasdegib is well tolerated and showed an elimination half-life compatible with a once-daily regimen. Currently, there are several ongoing studies including two phase II studies in patients with acute leukemia at high risk of relapse after donor stem cell transplant, and in myelofibrosis patients; and a phase I study in Japanese patients with select hematologic malignancies.

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