O04 - Tolerability and Efficacy of Adjuvant Temozolomide and Doxorubicin Combination Chemotherapy for Canine Splenic Hemangiosarcoma

Abstract: Background: Canine splenic hemangiosarcoma has an aggressive biologic behavior and short survival is common with standard-of-care splenectomy and adjuvant anthracycline chemotherapy.

Objectives: To evaluate tolerability and efficacy of adjuvant oral temozolomide in combination with standard-of-care treatment for canine splenic hemangiosarcoma

Animals: 18 client-owned dogs with splenic hemangiosarcoma

Methods: A prospective single-arm clinical trial was performed with 9 dogs enrolled to receive adjuvant doxorubicin-temozolomide chemotherapy (stage 1, n=1; 2, n=5; 3, n=3) and compared to 9 contemporaneous control dogs that received single-agent doxorubicin (stage 1, n=2; 2, n=4; 3, n=3). Doxorubicin (30 mg/m2 or 1 mg/kg) was administered intravenously every 21 days, followed by oral temozolomide (60 mg/m2) for 5 consecutive days.

Results: Median time to chemotherapy after splenectomy was 15 days (range 14-32). A median of 3 doxorubicin-temozolomide cycles were completed (range 1-5). Six dogs experienced grade 1 or 2 gastrointestinal toxicity, with grade 1 hyporexia most common (n=3). One episode of grade 3 anorexia was observed. Grade 1 hematologic toxicity occurred in 7 dogs, including anemia (n=4), neutropenia (n=5), and thrombocytopenia (n=1). Three dogs required a doxorubicin dose reduction, but none in temozolomide. Median progression-free survival was 98 days (95% CI 50-218) and median overall survival was 103 days (95% CI 50-218) in the doxorubicin-temozolomide group compared to 127 days (95% CI 22-222) and 156 days (95% CI 51-236) in the control group (p=0.723, p=0.530).

Conclusions: Results suggest that doxorubicin-temozolomide combination chemotherapy is tolerated, but not more efficacious than adjuvant doxorubicin in prolonging survival of dogs with splenic hemangiosarcoma.