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Evaluation of zoledronate for the treatment of canine stage III osteosarcoma: A phase II study

BACKGROUND: Greater than 90% of dogs with appendicular osteosarcoma will develop pulmonary metastasis despite the standard of care. Available treatments have limited efficacy for stage III disease. Zoledronate, a bisphosphonate, induces apoptosis of canine osteosarcoma cells and appears to modulate...

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Autores principales: Smith, Ashley A., Lindley, Stephanie E.S., Almond, Greg T., Bergman, Noelle S., Matz, Brad M., Smith, Annette N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9857128/
https://www.ncbi.nlm.nih.gov/pubmed/36398717
http://dx.doi.org/10.1002/vms3.1000
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author Smith, Ashley A.
Lindley, Stephanie E.S.
Almond, Greg T.
Bergman, Noelle S.
Matz, Brad M.
Smith, Annette N.
author_facet Smith, Ashley A.
Lindley, Stephanie E.S.
Almond, Greg T.
Bergman, Noelle S.
Matz, Brad M.
Smith, Annette N.
author_sort Smith, Ashley A.
collection PubMed
description BACKGROUND: Greater than 90% of dogs with appendicular osteosarcoma will develop pulmonary metastasis despite the standard of care. Available treatments have limited efficacy for stage III disease. Zoledronate, a bisphosphonate, induces apoptosis of canine osteosarcoma cells and appears to modulate the tumour microenvironment. OBJECTIVES: This prospective, single institutional phase IIa trial investigated the use of single agent zoledronate in dogs with pulmonary metastases from osteosarcoma. METHODS: Zoledronate was administered once monthly, and thoracic radiographs were used to assess response. RESULTS: Eleven dogs were enrolled. Stable disease was achieved in two of eight dogs available for response assessment. The median progression‐free survival was 28 days (range: 4–93 days). The median stage III‐specific survival time was 92 days. Adverse events were reported in four dogs; two dogs developed grade III or higher toxicities. Notable adverse events included conjunctivitis, fever, hypocalcaemia, and hypophosphatemia. CONCLUSIONS: Zoledronate appears to have limited efficacy as a single agent for stage III osteosarcoma and may be associated with unexpected toxicity in this population. This clinical trial was registered on the AVMA Animal Health Studies Database (AAHSD004396).
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spelling pubmed-98571282023-01-24 Evaluation of zoledronate for the treatment of canine stage III osteosarcoma: A phase II study Smith, Ashley A. Lindley, Stephanie E.S. Almond, Greg T. Bergman, Noelle S. Matz, Brad M. Smith, Annette N. Vet Med Sci DOGS BACKGROUND: Greater than 90% of dogs with appendicular osteosarcoma will develop pulmonary metastasis despite the standard of care. Available treatments have limited efficacy for stage III disease. Zoledronate, a bisphosphonate, induces apoptosis of canine osteosarcoma cells and appears to modulate the tumour microenvironment. OBJECTIVES: This prospective, single institutional phase IIa trial investigated the use of single agent zoledronate in dogs with pulmonary metastases from osteosarcoma. METHODS: Zoledronate was administered once monthly, and thoracic radiographs were used to assess response. RESULTS: Eleven dogs were enrolled. Stable disease was achieved in two of eight dogs available for response assessment. The median progression‐free survival was 28 days (range: 4–93 days). The median stage III‐specific survival time was 92 days. Adverse events were reported in four dogs; two dogs developed grade III or higher toxicities. Notable adverse events included conjunctivitis, fever, hypocalcaemia, and hypophosphatemia. CONCLUSIONS: Zoledronate appears to have limited efficacy as a single agent for stage III osteosarcoma and may be associated with unexpected toxicity in this population. This clinical trial was registered on the AVMA Animal Health Studies Database (AAHSD004396). John Wiley and Sons Inc. 2022-11-18 /pmc/articles/PMC9857128/ /pubmed/36398717 http://dx.doi.org/10.1002/vms3.1000 Text en © 2022 The Authors. Veterinary Medicine and Science published by John Wiley & Sons Ltd. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle DOGS
Smith, Ashley A.
Lindley, Stephanie E.S.
Almond, Greg T.
Bergman, Noelle S.
Matz, Brad M.
Smith, Annette N.
Evaluation of zoledronate for the treatment of canine stage III osteosarcoma: A phase II study
title Evaluation of zoledronate for the treatment of canine stage III osteosarcoma: A phase II study
title_full Evaluation of zoledronate for the treatment of canine stage III osteosarcoma: A phase II study
title_fullStr Evaluation of zoledronate for the treatment of canine stage III osteosarcoma: A phase II study
title_full_unstemmed Evaluation of zoledronate for the treatment of canine stage III osteosarcoma: A phase II study
title_short Evaluation of zoledronate for the treatment of canine stage III osteosarcoma: A phase II study
title_sort evaluation of zoledronate for the treatment of canine stage iii osteosarcoma: a phase ii study
topic DOGS
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9857128/
https://www.ncbi.nlm.nih.gov/pubmed/36398717
http://dx.doi.org/10.1002/vms3.1000
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