Safety evaluation of combination doxorubicin and toceranib phosphate (Palladia®) in tumour bearing dogs: a phase I dose‐finding study

Abstract

AbstractCombination chemotherapy holds promise for improving outcomes in malignancy when compared with single‐agent approaches. Care must be taken to avoid overlapping toxicity and to utilize agents with differing mechanisms of action. A phase I dose‐finding trial was performed to determine the maximally tolerated dose (MTD) of a concurrent toceranib and doxorubicin (DOX) combination protocol where toceranib dose was maintained at or near 2.75 mg kg−1by mouth every other day (PO EOD) while escalatingDOXdosage. The dose‐limiting toxicity was found to be neutropenia and theMTDof the combination was determined to be 25 mg m−2ofDOXq 21 days given concurrently with toceranib 2.75 mg kg−1PO EOD. This combination was well tolerated with no excessive gastrointestinal toxicity nor novel adverse events (AEs) noted. Anti‐tumour activity was observed in the majority of cases. This combination warrants further investigation in the context of phaseII/IIIclinical trials to characterize efficacy and long‐term AE profiles.