Introduction

Feline oral squamous cell carcinoma (FOSCC) is aggressively osteoinvasive and can be painful, with <10% one-year survival despite multi-modal therapies. Zoledronate (ZOL) is a potent bisphosphonate which reduces osteolysis and may have multiple mechanisms of radiosensitization. We hypothesized that combining ZOL with radiation therapy (RT) would be effective and well tolerated in pet cats with FOSCC and would decrease lysis.

Methods

To determine optimal timing, three FOSCC cell lines were treated with RT and ZOL at various time intervals. Cytotoxicity and clonogenicity were assessed using a sulforhodamine B assay and clonogenic assay, respectively. Pet cats with osteoinvasive OSCC were then treated with RT (8 Gy once weekly x 4, total 32 Gy) and ZOL (0.2 mg/kg IV q4w x 2). Volumetric and longest dimension tumor response was assessed using computed tomography (CT) scans at days 0 and 50. Safety and tolerability were monitored with hematologic and biochemical assessment, and acute radiation adverse effects were characterized using VRTOG criteria. Serum CTx, a marker of bone-resorption, was measured weekly.

Results

In vitro data revealed no clear effect on timing, therefore, ZOL was given immediately prior to RT as is customary with traditional radiosensitizing agents. All 9 patients received the full treatment protocol. Evaluable responses included 1 CR, 3 PR, and 2 SD. Treatment was tolerated well in all cats with minimal RT toxicity and no ZOL toxicity. Serum CTx decreased over time in all patients.

Conclusion

Combining RT with ZOL in cats with FOSCC is safe, well-tolerated, and reduces bone resorption.

Funding Information

This work was funded by the Companion Animal Memorial Fund from the College of Veterinary Medicine at the University of Illinois at Urbana-Champaign.