title: Safety evaluation of combination toceranib phosphate (Palladia®) and piroxicam in tumour-bearing dogs (excluding mast cell tumours): a phase I dose-finding study.
abstract: 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.
authors.affiliation: Department of Medical Sciences, School of Veterinary Medicine, Madison, WI, USA.
authors.forename: E
authors.initials: E
authors.lastname: Chon
authors.forename: L
authors.initials: L
authors.lastname: McCartan
authors.forename: L N
authors.initials: LN
authors.lastname: Kubicek
authors.forename: D M
authors.initials: DM
authors.lastname: Vail
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / 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; D004359:Drug Therapy, Combination; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced / Q000662:veterinary; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D009369:Neoplasms / Q000188:drug therapy / Q000662:veterinary*; D010894:Piroxicam / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011758:Pyrroles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D010894:Piroxicam; C464577:toceranib phosphate; D011505:Protein-Tyrosine Kinases