title: Toxicity and response in cats with neoplasia treated with toceranib phosphate.
abstract: Objectives Toceranib phosphate is a tyrosine kinase inhibitor licensed for the treatment of non-resectable Patnaik grade II/III recurrent cutaneous mast cell tumours in dogs. There is no information in cats regarding the tolerated dose, toxicity or tumour response of this drug. The aim of this study was to analyse retrospectively a cohort of cats with advanced neoplasia treated with toceranib to identify toxicity and response. Methods The medical records of the Small Animal Teaching Hospital were reviewed. Cats were included if they had received toceranib for at least 2 weeks for the treatment of histologically or cytologically confirmed neoplastic disease, and had at least one set of monitoring blood tests (haematology, biochemistry) performed after baseline tests. Toxicity was graded according to the Veterinary Comparative Oncology Group - common terminology criteria for adverse events(VCOG-CTCAE) and response was measured according to Response Evaluation In Solid Tumors (RECIST) criteria. Results Fourteen cats met the inclusion criteria, the majority of which (13/14) had received previous therapy (surgery, radiotherapy, chemotherapy). The most common tumour types were mast cell tumours or malignant epithelial tumours. Toxicity occurred in 10/14 cats - 10 cats had mild myelosuppression or gastrointestinal effects. Two cats developed severe hepatoxicity. One cat died from congestive heart failure, although whether this was related to toceranib therapy is unknown. Regarding response, one cat achieved complete response; two cats achieved partial response and five cats achieved stable disease: overall biological response rate was 57.1%. All of the cats that achieved either partial or complete response were treated for mast cell disease. Overall median duration of response was 90 days (range 14-570 days). None of the cats with squamous cell carcinoma achieved a response. Conclusions and relevance Toceranib phosphate is generally well tolerated in cats, with toxicity limited to mild gastrointestinal or myelosuppressive effects in the majority of cases (10/14) in this study; however, hepatotoxicity is a concern. Response to treatment in this small cohort was similar to that reported in dogs.
authors.affiliation: Department of Veterinary Medicine, University of Liverpool, Liverpool, UK.
authors.forename: Aaron
authors.initials: A
authors.lastname: Harper
authors.affiliation: Department of Veterinary Medicine, University of Liverpool, Liverpool, UK.
authors.forename: Laura
authors.initials: L
authors.lastname: Blackwood
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000662:veterinary*; D002371:Cat Diseases / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002415:Cats; D015331:Cohort Studies; D005260:Female; D007211:Indoles / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D008297:Male; D011758:Pyrroles / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000188:drug therapy / Q000662:veterinary*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; C464577:toceranib phosphate