Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/21616
Title: Auranofin improves overall survival when combined with standard of care in a pilot study involving dogs with osteosarcoma.
Austin Authors: Endo-Munoz, Liliana;Bennett, Tristram C;Topkas, Eleni;Wu, Sherry Y;Thamm, Douglas H;Brockley, Laura;Cooper, Maureen;Sommerville, Scott;Thomson, Maurine;O'Connell, Kathleen;Lane, Amy;Bird, Guy;Peaston, Anne;Matigian, Nicholas;Straw, Rodney C;Saunders, Nicholas A
Affiliation: Flint Animal Cancer Center, Colorado State University, Fort Collins, Colorado, USA
Veterinary Specialist Services, Brisbane, Queensland, Australia
Department of Orthopedic Oncology, Princess Alexandra Hospital and The Wesley Hospital, Brisbane, Queensland, Australia
Victorian Animal Cancer Care, Melbourne, Victoria, Australia
School of Biomedical Sciences, University of Queensland, St Lucia, Queensland, Australia
Brisbane Veterinary Specialist Centre, Brisbane, Queensland, Australia
The University of Queensland Diamantina Institute, The University of Queensland, Translational Research Institute, Brisbane, Queensland
Australian Consortium of Comparative Oncology of the Australian Animal Cancer Foundation, Brisbane, Queensland, Australia
QFAB Bioinformatics, BIODATA Institute of Molecular Bioscience, The University of Queensland, Brisbane, Australia
School of Animal and Veterinary Sciences, The University of Adelaide, Adelaide, South Australia, Australia
Veterinary Emergency Centre and Hospital, James Cook University School of Veterinary and Biomedical Science, Townsville, Queensland, Australia
Small Animal Oncology, Newcastle, New South Wales, Australia
Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
School of Cancer Medicine, La Trobe University, Melbourne, Victoria, Australia
Issue Date: Jun-2020
metadata.dc.date: 2019-08-23
Publication information: Veterinary and comparative oncology 2020; 18(2): 206-213
Abstract: Osteosarcoma is the most common pediatric primary bone malignancy. The major cause of death in osteosarcoma is drug-resistant pulmonary metastasis. Previous studies have shown that thioredoxin reductase 2 is a driver of metastasis in osteosarcoma and can be inhibited by auranofin. Moreover, studies have shown that auranofin significantly reduces pulmonary metastases in xenotransplant models.1 Here we describe a phase I/II study of auranofin in canine osteosarcoma, a well-recognized spontaneous model of human osteosarcoma. We performed a single arm multicenter pilot study of auranofin in combination with standard-of-care (amputation + carboplatin). We recruited 40 dogs to the trial and used a historical standard-of-care-only control group (n = 26). Dogs >15 kg received 9 mg auranofin q3d PO and dogs <15 kg received 6 mg q3d. Follow-up occurred over at least a 3 year period. Auranofin plus standard-of-care improved overall survival (P = 0.036) in all dogs treated. The improved outcome was attributable entirely to improved overall survival in male dogs (P = 0.009). At the time of writing, ten dogs (25%) survive without measurable disease in the treatment group with survival times ranging between 806 and 1525 days. Our study shows that auranofin improves overall survival in male dogs when combined with standard-of-care. Our findings have translational relevance for the management of canine and human osteosarcoma. Our data justify a larger multicentre phase 2 trial in dogs and a phase I/II trial in human patients with refractory disease at the time of initial surgery. This article is protected by copyright. All rights reserved.
URI: http://ahro.austin.org.au/austinjspui/handle/1/21616
DOI: 10.1111/vco.12533
ORCID: 0000-0002-7501-2415
0000-0002-2478-3420
PubMed URL: 31441983
Type: Journal Article
Subjects: auranofin
clinical trial
metastasis
osteosarcoma
thioredoxin reductase 2
Appears in Collections:Journal articles

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