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Safety evaluation of combination doxorubicin and toceranib phosphate (Palladia®) in tumour bearing dogs: a phase I dose‐finding study |
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| Authors: | M. A. Pellin R. M. Wouda K. Robinson K. Tsimbas I. D. Kurzman B. J. Biller D. M. Vail |
| Affiliation: | 1. Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin‐Madison, Madison, WI, USA;2. Kansas State University, College of Veterinary Medicine, Manhattan, KS, USA;3. Flint Animal Cancer Center, Colorado State University, Fort Collins, CO, USA;4. Carbone Cancer Center, University of Wisconsin‐Madison, Madison, WI, USA |
| Abstract: | Combination 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?1 by mouth every other day (PO EOD) while escalating DOX dosage. The dose‐limiting toxicity was found to be neutropenia and the MTD of the combination was determined to be 25 mg m?2 of DOX q 21 days given concurrently with toceranib 2.75 mg kg?1 PO 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 phase II/III clinical trials to characterize efficacy and long‐term AE profiles. |
| Keywords: | cancer canine chemotherapy doxorubicin toceranib Tregs |