@article{8ca14ec026784d6f8e9c07941563f789,
title = "Phase 1 dose escalation trial of volasertib in combination with decitabine in patients with acute myeloid leukemia",
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.",
keywords = "AML, Decitabine, PLK1, Phase 1, Volasertib",
author = "Jorge Cortes and Nikolai Podoltsev and Hagop Kantarjian and Gautam Borthakur and Zeidan, {Amer M.} and Maximilian Stahl and Tillmann Taube and Nora Fagan and Sushmita Rajeswari and Uy, {Geoffrey L.}",
note = "Funding Information: J. C. has received research support from Boehringer Ingelheim, Bristol-Myers Squibb, Novartis, Pfizer, Jazz Pharmaceuticals, Astellas Pharma, Daiichi Sankyo, ImmunoGen, Merus, and Arog Pharmaceuticals, and acted as a consultant for Bristol-Myers Squibb, Novartis, Pfizer, Jazz Pharmaceuticals, Astellas Pharma, and Daiichi Sankyo. N. P. consulted for and received honoraria from Alexion Pharmaceuticals, Pfizer, CTi BioPharma, Agios Pharmaceuticals, Blueprint Medicines, Incyte, Novartis, and Celgene, received research grants from Celgene, and institution funding for administration of clinical trials from Boehringer Ingelheim, Astellas Pharma, Daiichi Sankyo, Sunesis Pharmaceuticals, Celator Pharmaceuticals, Pfizer, Astex Pharmaceuticals, CTi Biopharma, Genentech, AI Therapeutics, Samus Therapeutics, Arog Pharmaceuticals, and Kartos Therapeutics. H. K. has received research grants from AbbVie, Agios Pharmaceuticals, Amgen, Ariad Pharmaceuticals, Astex Pharmaceuticals, Bristol-Myers Squibb, Cyclacel, Daiichi Sankyo, Immunogen, Jazz Pharmaceuticals, Novartis, Pfizer, and honoraria from AbbVie, Actinium Pharmaceuticals (Advisory Board), Agios Pharmaceuticals, Amgen, Immunogen, Orsinex, Pfizer, and Takeda. A. M. Z. is a Leukemia and Lymphoma Society Scholar in Clinical Research and is also supported by a NCI{\textquoteright}s Cancer Clinical Investigator Team Leadership Award (CCITLA). A. M. Z. received research funding (institutional) from Celgene, Acceleron, Abbvie, Otsuka, Pfizer, Medimmune/AstraZeneca, Boehringer Ingelheim, Trovagene, Incyte, Takeda, and ADC Therapeutics. A.M.Z. had a consultancy with and received honoraria from AbbVie, Otsuka, Pfizer, Celgene, Jazz, Ariad, Incyte, Agios, Boehringer-Ingelheim, Novartis, Acceleron, Astellas, Daiichi Sankyo, Cardinal Health, Seattle Genetics, BeyondSpring, and Takeda. None of these relationships were related to the development of this manuscript. T. T. is an employee of Boehringer Ingelheim International GmbH. N. F. and S. R. are employees of Boehringer Ingelheim Pharmaceuticals, Inc. G. L. U. has received honoraria from Boehringer Ingelheim, Astellas Pharma, and Pfizer. G. B. and M. S. have no conflicts of interest to declare. 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: {\textcopyright} 2020, Japanese Society of Hematology.",
year = "2021",
month = jan,
doi = "10.1007/s12185-020-02994-8",
language = "English (US)",
volume = "113",
pages = "92--99",
journal = "International Journal of Hematology",
issn = "0925-5710",
publisher = "Springer Japan",
number = "1",
}
