TY - JOUR
T1 - Phase i study assessing the safety and tolerability of barasertib (azd1152) with low-dose cytosine arabinoside in elderly patients with AML
AU - Kantarjian, Hagop M.
AU - Sekeres, Mikkael A.
AU - Ribrag, Vincent
AU - Rousselot, Philippe
AU - Garcia-Manero, Guillermo
AU - Jabbour, Elias J.
AU - Owen, Kate
AU - Stockman, Paul K.
AU - Oliver, Stuart D.
N1 - Funding Information:
Dr. Kantarjian has received research grants from AstraZeneca; Dr. Sekeres has attended advisory boards for Celgene and Amgen; Dr. Ribrag has received research support from Servier , Bayer , and Sanofi , and has served as a consultant for Takeda, Servier, and AstraZeneca; Drs Owen, Stockman, and Oliver are employees of and own stock in AstraZeneca. All other authors have no conflicts of interest.
PY - 2013/10
Y1 - 2013/10
N2 - Introduction: Barasertib is the pro-drug of barasertib-hydroxy-quinazoline pyrazole anilide, a selective Aurora B kinase inhibitor that has demonstrated preliminary anti-AML activity in the clinical setting. Patients and Methods: This Phase I dose-escalation study evaluated the safety and tolerability of barasertib, combined with LDAC, in patients aged 60 years or older with de novo or secondary AML. Barasertib (7-day continuous intravenous infusion) plus LDAC 20 mg (subcutaneous injection twice daily for 10 days) was administered in 28-day cycles. The MTD was defined as the highest dose at which ≤ 1 patient within a cohort of 6 experienced a dose-limiting toxicity (DLT) (clinically significant adverse event [AE] or laboratory abnormality considered related to barasertib). The MTD cohort was expanded to 12 patients. Results: Twenty-two patients (median age, 71 years) received ≥ 1 treatment cycle (n = 6, 800 mg; n = 13, 1000 mg; n = 3, 1200 mg). DLTs were reported in 2 patients (both, National Cancer Institute Common Terminology Criteria for Adverse Events grade 3 stomatitis/mucositis; 1200 mg cohort). The most common AEs were infection (73%), febrile neutropenia (59%), nausea (50%), and diarrhea (46%). Barasertib plus LDAC resulted in an overall response rate (International Working Group criteria) of 45% (n = 10/22; according to investigator opinion). Conclusion: The MTD of 1000 mg barasertib in combination with LDAC in older patients with AML was associated with acceptable tolerability and preliminary anti-AML activity.
AB - Introduction: Barasertib is the pro-drug of barasertib-hydroxy-quinazoline pyrazole anilide, a selective Aurora B kinase inhibitor that has demonstrated preliminary anti-AML activity in the clinical setting. Patients and Methods: This Phase I dose-escalation study evaluated the safety and tolerability of barasertib, combined with LDAC, in patients aged 60 years or older with de novo or secondary AML. Barasertib (7-day continuous intravenous infusion) plus LDAC 20 mg (subcutaneous injection twice daily for 10 days) was administered in 28-day cycles. The MTD was defined as the highest dose at which ≤ 1 patient within a cohort of 6 experienced a dose-limiting toxicity (DLT) (clinically significant adverse event [AE] or laboratory abnormality considered related to barasertib). The MTD cohort was expanded to 12 patients. Results: Twenty-two patients (median age, 71 years) received ≥ 1 treatment cycle (n = 6, 800 mg; n = 13, 1000 mg; n = 3, 1200 mg). DLTs were reported in 2 patients (both, National Cancer Institute Common Terminology Criteria for Adverse Events grade 3 stomatitis/mucositis; 1200 mg cohort). The most common AEs were infection (73%), febrile neutropenia (59%), nausea (50%), and diarrhea (46%). Barasertib plus LDAC resulted in an overall response rate (International Working Group criteria) of 45% (n = 10/22; according to investigator opinion). Conclusion: The MTD of 1000 mg barasertib in combination with LDAC in older patients with AML was associated with acceptable tolerability and preliminary anti-AML activity.
KW - Acute myeloid leukemia
KW - Barasertib-hQPA
KW - Dose-escalation study
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U2 - 10.1016/j.clml.2013.03.019
DO - 10.1016/j.clml.2013.03.019
M3 - Article
C2 - 23763917
AN - SCOPUS:84884155615
SN - 2152-2650
VL - 13
SP - 559
EP - 567
JO - Clinical Lymphoma, Myeloma and Leukemia
JF - Clinical Lymphoma, Myeloma and Leukemia
IS - 5
ER -