Metronomic therapy with cyclophosphamide and piroxicam effectively delays tumor recurrence in dogs with incompletely resected soft tissue sarcomas.
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.


OBJECTIVE
We hypothesized that continuous treatment with low-dose cyclophosphamide and full-dose piroxicam would delay tumor recurrence in dogs with soft tissue sarcomas (STS).


METHODS
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.
Elmslie
R E
RE
Veterinary Cancer Specialists, Englewood, CO, USA.
Glawe
P
P
Dow
S W
SW
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004283:Dog Diseases / Q000188:drug therapy*; D004285:Dogs; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control / Q000601:surgery / Q000662:veterinary*; D010894:Piroxicam / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012189:Retrospective Studies; D012509:Sarcoma / Q000517:prevention & control / Q000601:surgery / Q000662:veterinary*; D012983:Soft Tissue Neoplasms / Q000517:prevention & control / Q000601:surgery / Q000662:veterinary*
D010894:Piroxicam; D003520:Cyclophosphamide