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.

Management of a feline gastric stromal cell tumour with toceranib phosphate: a case study

“…The most commonly reported side effect of toceranib in cats is anorexia, with diarrhoea and vomiting seen in 25%–30% of cats; however, two reports noted severe hepatotoxicity associated with serum alkaline phosphatase or alanine transaminase elevations in 6 of 32 cats . Another study showed although 60% of cats had some side effects, nearly 90% were low grade and resolved without direct intervention .…”

“…Toceranib (Palladia; Zoetis) is licensed for the treatment of cutaneous mast cell tumours in dogs. Off‐label usage in cats has been described for a variety of tumour types including oral squamous cell carcinoma, injection site sarcoma, mast cell neoplasia and pancreatic carcinoma . In cats, the most common toxicities of toceranib include mild gastrointestinal signs and myelosuppression which are self‐limiting or resolve with a dose adjustment or treatment break.…”

External beam radiotherapy for the treatment of feline salivary gland carcinoma: six new cases and a review of the literature

“…In addition, combining chemotherapy with RT for humans with high-risk salivary gland carcinomas (ie, those with large and invasive primary tumours, close or incomplete margins, high histopathological grade, histological evidence of neural or vascular invasion, or positive lymph nodes) does not offer survival benefit but does increase morbidity, so is not recommended. 31 Toceranib phosphate has been used in cats with a variety of malignancies, including carcinomas and adenocarcinomas, and is generally well tolerated, [32][33][34] but data on response are limited. The short median durations of treatment (40, 77 and 100 days, respectively) [32][33][34] in the toxicity studies suggest that there is often relatively rapid disease progression.…”

Tumour angiogenesis, anti‐angiogenic therapy and chemotherapeutic resistance

“…Toceranib and masitinib have been approved for veterinary use in dogs, particularly for mast cell tumours . However, a range of anti‐angiogenic drugs, either alone or in combination, has been used to treat a wide variety of canine and feline neoplasms, including osteosarcomas, melanomas, fibrosarcomas, histiocytic sarcomas, haemangiosarcomas, lymphomas and prostatic, thyroid, nasal, gastric, mammary, pulmonary, biliary, salivary, anal sac and urinary bladder carcinomas …”

“…In the majority of these veterinary studies, tocerinab was used, sometimes alone [29][30][31][32][33][34][35][36][37] or, more commonly, in combination with other drugs such as cyclophosphamide (belonging to the nitrogen mustard group of alkylating agents), 38,39 vinblastine (an antimitotic alkaloid), 40,41 carboplatin (a platinum-containing complex), 42,43 lomustine (1-(2-chloroethyl)-3-cyclohexyl-1-nitrosurea (or CCNU), which belongs to the nitrosurea group of alkylating agents), [44][45][46] doxorubicin (an anthracycline antibiotic) [47][48][49] and piroxicam (a nonsteroidal anti-inflammatory drug (NSAID) with cyclooxygenase (COX)-2 inhibiting properties). 38,[50][51][52] Masitinib has also been evaluated in dogs.…”