TY - JOUR
T1 - Phase 1 dose escalation trial of volasertib in combination with decitabine in patients with acute myeloid leukemia
AU - Cortes, Jorge
AU - Podoltsev, Nikolai
AU - Kantarjian, Hagop
AU - Borthakur, Gautam
AU - Zeidan, Amer M.
AU - Stahl, Maximilian
AU - Taube, Tillmann
AU - Fagan, Nora
AU - Rajeswari, Sushmita
AU - Uy, Geoffrey L.
N1 - Funding Information:
Financial support for this study was provided by Boehringer Ingelheim. Research reported in this publication was in part supported by the National Cancer Institute of the National Institutes of Health under Award Number P30 CA016359. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Medical writing assistance, financially supported by Boehringer Ingelheim, was provided by Christina Jennings of GeoMed, an Ashfield company, part of UDG Healthcare plc, during the preparation of this manuscript.
Publisher Copyright:
© 2020, Japanese Society of Hematology.
PY - 2021/1
Y1 - 2021/1
N2 - Polo-like kinase 1 (PLK1) regulates mitotic checkpoints and cell division. PLK1 overexpression is reported in numerous cancers, including acute myeloid leukemia (AML), and is associated with poor prognosis. Volasertib is a selective, potent cell-cycle kinase inhibitor that targets PLK to induce mitotic arrest and apoptosis. This phase 1 trial investigated the maximum tolerated dose (MTD), safety, pharmacokinetics, and anti-leukemic activity of volasertib in combination with decitabine in AML patients aged ≥ 65 years. Thirteen patients were treated with escalating volasertib doses (3 + 3 design; 300 mg, 350 mg, and 400 mg) plus standard-dose decitabine. Dose-limiting toxicity was reported in one patient in cycle 1; the MTD of volasertib in combination with decitabine was determined as 400 mg. The most common treatment-emergent adverse events were febrile neutropenia, pneumonia, and decreased appetite. Objective response rate was 23%. The combination was well tolerated, and the adverse event profile was in line with previous findings.
AB - Polo-like kinase 1 (PLK1) regulates mitotic checkpoints and cell division. PLK1 overexpression is reported in numerous cancers, including acute myeloid leukemia (AML), and is associated with poor prognosis. Volasertib is a selective, potent cell-cycle kinase inhibitor that targets PLK to induce mitotic arrest and apoptosis. This phase 1 trial investigated the maximum tolerated dose (MTD), safety, pharmacokinetics, and anti-leukemic activity of volasertib in combination with decitabine in AML patients aged ≥ 65 years. Thirteen patients were treated with escalating volasertib doses (3 + 3 design; 300 mg, 350 mg, and 400 mg) plus standard-dose decitabine. Dose-limiting toxicity was reported in one patient in cycle 1; the MTD of volasertib in combination with decitabine was determined as 400 mg. The most common treatment-emergent adverse events were febrile neutropenia, pneumonia, and decreased appetite. Objective response rate was 23%. The combination was well tolerated, and the adverse event profile was in line with previous findings.
KW - AML
KW - Decitabine
KW - PLK1
KW - Phase 1
KW - Volasertib
UR - http://www.scopus.com/inward/record.url?scp=85091166720&partnerID=8YFLogxK
U2 - 10.1007/s12185-020-02994-8
DO - 10.1007/s12185-020-02994-8
M3 - Article
C2 - 32951163
AN - SCOPUS:85091166720
SN - 0925-5710
VL - 113
SP - 92
EP - 99
JO - International Journal of Hematology
JF - International Journal of Hematology
IS - 1
ER -