Safety evaluation of combination toceranib phosphate (Palladia®) and piroxicam in tumour‐bearing dogs (excluding mast cell tumours): a phase I dose‐finding study

Toceranib phosphate and piroxicam have individually demonstrated antineoplastic activity. Additionally, non‐steroidal anti‐inflammatory therapy is often warranted in aged cancer‐bearing dogs for management of osteoarthritis comorbidity. As concurrent use may be warranted for a given individual and the adverse event (AE) profile for each can be overlapping (gastrointestinal), a phase I trial was performed in tumour‐bearing (non‐mast cell) dogs to establish the safety of the combination using a standard 3+3 cohort design. Five dose‐escalating cohorts, up to and including approved label dosage for toceranib and standard dosage for piroxicam, were completed without observing a frequency of dose‐limiting AEs necessitating cohort closure. Therefore, the combination of standard dosages of both drugs (toceranib, 3.25 mg kg −1 , every other day; piroxicam, 0.3 mg kg −1 daily) is generally safe. Several antitumour responses were observed. As with single‐agent toceranib, label‐indicated treatment holidays and dose reductions (e.g. 2.5–2.75 mg kg −1 ) may occasionally be required owing to gastrointestinal events.