Phase 1 dose escalation trial of volasertib in combination with decitabine in patients with acute myeloid leukemia.
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Abstract | :
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. |
Year of Publication | :
2021
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Journal | :
International journal of hematology
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Volume | :
113
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Issue | :
1
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Number of Pages | :
92-99
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ISSN Number | :
0925-5710
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URL | :
https://dx.doi.org/10.1007/s12185-020-02994-8
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DOI | :
10.1007/s12185-020-02994-8
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Short Title | :
Int J Hematol
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