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

Abstract

Abstract 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).

Keywords

• bisphosphonate
• bone
• lung
• zoledronic acid