Title |
Phase II study of the oral selective inhibitor of nuclear export (SINE) KPT-335 (verdinexor) in dogs with lymphoma
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Published in |
BMC Veterinary Research, August 2018
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DOI | 10.1186/s12917-018-1587-9 |
Pubmed ID | |
Authors |
Abbey R. Sadowski, Heather L. Gardner, Antonella Borgatti, Heather Wilson, David M. Vail, Joshua Lachowicz, Christina Manley, Avenelle Turner, Mary K. Klein, Angharad Waite, Alexandra Sahora, Cheryl A. London |
Abstract |
Chemotherapeutic options for the treatment of canine lymphoma have not changed in several decades necessitating the identification of new therapeutics to improve patient outcome. KPT-335 (verdinexor) is a novel orally bioavailable selective inhibitor of nuclear export (SINE) that exhibited anti-tumor activity against non-Hodgkin lymphoma in a prior phase I study. The objective of this phase II study was to expand upon the initial findings and assess the activity and safety in a larger population of dogs with lymphoma. Fifty-eight dogs with naïve or progressive B-cell and T-cell lymphoma were enrolled in this clinical trial. KPT-335 was administered orally in one of three dosing groups, based on the previously established biologically active dose of 1.5 mg/kg three times weekly. Treatment with single-agent, orally administered KPT-335 resulted in an objective response rate (ORR) of 37%, of which dogs with T-cell lymphoma had an ORR of 71%. KPT-335 was well tolerated in all dose groups with grade 1-2 anorexia being the most common adverse event. Anorexia was responsive to symptomatic and supportive medications, including prednisone. These data demonstrate that KPT-335 has biologic activity in canine lymphoma, and support continued evaluation of SINE compounds such as KPT-335 in combination with standard chemotherapeutics in canine lymphoma. |
X Demographics
Geographical breakdown
Country | Count | As % |
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Italy | 2 | 20% |
United States | 1 | 10% |
Unknown | 7 | 70% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 9 | 90% |
Practitioners (doctors, other healthcare professionals) | 1 | 10% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 70 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Researcher | 14 | 20% |
Student > Master | 7 | 10% |
Other | 5 | 7% |
Student > Doctoral Student | 4 | 6% |
Student > Postgraduate | 4 | 6% |
Other | 12 | 17% |
Unknown | 24 | 34% |
Readers by discipline | Count | As % |
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Veterinary Science and Veterinary Medicine | 26 | 37% |
Medicine and Dentistry | 6 | 9% |
Biochemistry, Genetics and Molecular Biology | 5 | 7% |
Psychology | 2 | 3% |
Nursing and Health Professions | 1 | 1% |
Other | 8 | 11% |
Unknown | 22 | 31% |