title: Safety evaluation of combination doxorubicin and toceranib phosphate (Palladia®) in tumour bearing dogs: a phase I dose-finding study.
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-1by 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-2of DOX q 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 phase II/III clinical trials to characterize efficacy and long-term AE profiles.
authors.affiliation: Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Pellin
authors.affiliation: Kansas State University, College of Veterinary Medicine, Manhattan, KS, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Wouda
authors.affiliation: Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: K
authors.initials: K
authors.lastname: Robinson
authors.affiliation: Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: K
authors.initials: K
authors.lastname: Tsimbas
authors.affiliation: Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: I D
authors.initials: ID
authors.lastname: Kurzman
authors.affiliation: Flint Animal Cancer Center, Colorado State University, Fort Collins, CO, USA.
authors.forename: B J
authors.initials: BJ
authors.lastname: Biller
authors.affiliation: Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, USA.|Carbone Cancer Center, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: D M
authors.initials: DM
authors.lastname: Vail
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D004283:Dog Diseases / Q000188:drug therapy*; D004285:Dogs; D004317:Doxorubicin / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D004334:Drug Administration Schedule / Q000662:veterinary; D004359:Drug Therapy, Combination / Q000662:veterinary; D005260:Female; D005434:Flow Cytometry / Q000662:veterinary; D007211:Indoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D009369:Neoplasms / Q000188:drug therapy / Q000662:veterinary*; D009503:Neutropenia / Q000139:chemically induced / Q000662:veterinary; D011758:Pyrroles / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; C464577:toceranib phosphate; D004317:Doxorubicin
keywords: Tregs; cancer; canine; chemotherapy; doxorubicin; toceranib