Duska, Linda R.
Petroni, Gina R.
Lothamer, Heather
Faust, William Jr.
Beumer, Jan H.
Christner, Susan M.
Mills, Anne M.
Fracasso, Paula M.
Parsons, Sarah J.
Funding for this research was provided by:
National Cancer Institute (P30 CA44579)
Article History
Received: 13 August 2018
Accepted: 3 December 2018
First Online: 8 December 2018
Compliance with ethical standards
:
: Linda R. Duska, Gina R. Petroni, Heather Lothamer, William Faust, Susan M. Christner, Anne M. Mills, and Sarah J. Parsons have no financial conflicts of interest. Dr. Duska receives research funding to her department (OB/GYN) for clinical trial research. Jan Beumer reports receiving research funding from BMS to his institute. Dr. Fracasso reports that she became an employee of Bristol-Myers Squibb Company (BMS) as of May 1, 2014, and as such, she has stock with the company. Prior to her employment with BMS, she was a Professor of Medicine and Obstetrics and Gynecology at the University of Virginia where she is now affiliated as a Visiting Professor of Medicine and Obstetrics and Gynecology. This clinical study was done while she was a Professor at the University of Virginia and no activities in this work have any relationship to her work at BMS.
: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
: Informed consent was obtained from all individual participants included in the study.
: Window-of-opportunity trials represent a relatively novel trial mechanism designed to ask translational questions about drug mechanism without intention of clinical benefit. In the case of endometrial cancer, the penultimate “biopsy” is the surgical specimen, allowing study of the tumor tissue as well as the adjacent normal endometrium, the endometrial stroma (the microenvironment) and the myometrium. Prior surgical window studies in endometrial cancer have demonstrated the feasibility and acceptability of this trial format. These studies allow investigators to answer complex scientific questions regarding drug mechanism of action in the tumor, as well as pharmacokinetic and pharmacodynamic questions. In the current study, we demonstrated for the first time that dasatinib was measurable and concentrated in tumor tissue 8 hours after dosing. Additionally, we demonstrated drug activity in tumor and normal tissue. These findings will allow further study of dasatinib in solid tumor, as well as inform future trials.