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

Abstract

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