Evaluation of toxicities from combined metronomic and maximal-tolerated dose chemotherapy in dogs with osteosarcoma.

Objective: To evaluate the tolerability of a piroxicam and cyclophosphamide metronomic treatment protocol combined with carboplatin alone or carboplatin and doxorubicin at maximal-tolerated doses.

Methods: Retrospective study of 30 dogs diagnosed with osteosarcoma. All dogs underwent amputation and chemotherapy treatment with one of the two maximal-tolerated dose protocols. Metronomic chemotherapy was administered in conjunction with these protocols, and continued subsequently. The protocols included 0 · 3 mg/kg piroxicam and 10 to 12 mg/M(2) cyclophosphamide with 300 mg/M(2) carboplatin alone, or 300 mg/M(2) carboplatin alternating with 30 mg/M(2) doxorubicin.

Results: Fourteen dogs were treated with the carboplatin and metronomic protocol and 16 were treated with the carboplatin alternating with doxorubicin and metronomic protocol. Grades 3 and 4 toxicities overall were significantly (P = 0 · 018) more common in the former group. The disease-free interval of the carboplatin and metronomic group was 192 days, which was not significantly different (P = 0 · 916) to the 182 days for the carboplatin alternating with doxorubicin and metronomic group. The median survival times of the two groups were 217 and 189 days, respectively.

Clinical Significance: Piroxicam and cyclophosphamide metronomic protocols can be safely administered in combination with maximal-tolerated dose chemotherapy protocols. A significantly higher frequency of toxicities was observed in dogs treated with the carboplatin and metronomic protocol.