Metronomic Therapy with Cyclophosphamide and Piroxicam Effectively Delays Tumor Recurrence in Dogs with Incompletely Resected Soft Tissue Sarcomas
Article first published online: 3 OCT 2008
Copyright © 2008 by the American College of Veterinary Internal Medicine
Journal of Veterinary Internal Medicine
Volume 22, Issue 6, pages 1373–1379, November–December 2008
How to Cite
Elmslie, R.E., Glawe, P. and Dow, S.W. (2008), Metronomic Therapy with Cyclophosphamide and Piroxicam Effectively Delays Tumor Recurrence in Dogs with Incompletely Resected Soft Tissue Sarcomas. Journal of Veterinary Internal Medicine, 22: 1373–1379. doi: 10.1111/j.1939-1676.2008.0179.x
- Issue published online: 30 OCT 2008
- Article first published online: 3 OCT 2008
- Submitted November 21, 2007; Revised February 18, 2008; Accepted August 25, 2008.
Background: Continuous administration of low doses of cyclophosphamide and standard doses of cyclooxygenase-inhibiting drugs has been shown to suppress tumor angiogenesis, reverse immunosuppression, and deplete regulatory T cells in cancer models.
Hypothesis: We hypothesized that continuous treatment with low-dose cyclophosphamide and full-dose piroxicam would delay tumor recurrence in dogs with soft tissue sarcomas (STS).
Animals: Eighty-five dogs with incompletely resected STS, 30 treated dogs, and 55 contemporary control dogs.
Methods: Treatment outcomes in 85 dogs with incompletely resected STS were evaluated in a retrospective study. Dogs in the treatment group received continuously administered low-dose cyclophosphamide (10 mg/m2) and standard dose piroxicam (0.3 mg/kg) therapy. Time to local tumor recurrence (disease-free interval; DFI) was compared between the 30 treated dogs and 55 untreated control dogs matched for age and tumor site and grade.
Results: DFI was significantly (P < .0001) prolonged for STS of all sites (trunk and extremity) in treated dogs compared with untreated control dogs. The DFI also was significantly longer in treated dogs when tumor site (trunk and extremity) was compared. Twelve treated dogs (40%) experienced mild toxicity (grade 1 and 2) at some point during treatment and 1 dog developed grade 4 cystitis. Every other day dosing was tolerated better than daily dosing.
Conclusions: Metronomic therapy with cyclophosphamide and piroxicam was very effective in preventing tumor recurrence in dogs with incompletely resected STS. These findings suggest that further evaluation of this approach is warranted as adjuvant therapy in dogs with highly metastatic tumors such as osteosarcoma and melanoma.