SAFETY EVALUATION OF COMBINATION DOXORUBICIN AND TOCERANIB PHOSPHATE (PALLADIA(R)) IN TUMOR BEARING DOGS: A PHASE I DOSE FINDING STUDY (VCS Award Winner)

摘要

Combination chemotherapy holds the promise of improved outcome in canine malignancy, but care must be taken to avoid overlapping toxicity.Dogs with cytologically or histologically diagnosed tumors of any histology (excluding mast cell tumors) and any stage were allowed. A standard, open-label, phase I, 3+3 dose-cohort escalation design was employed. The toceranib dose remained constant at2.75 mg/kg administered orally every other day. Doxorubicin was initiated at 20mg/m2 administered IV every 21 days for four doses. The doxorubicin dose was escalated by 5 mg/m2 each cohort until MTD or 30mg/m2 was reached. DLT was defined as any grade 3adverse event with the exception of hematopoietic AEs for which a grade 4 AE was considered dose limiting. Any grade AE that was refractory to supportive care or persisted beyond seven days was also considered dose-limiting.