Toceranib phosphate in the treatment of canine thyroid carcinoma: 42 cases (2009‐2018)

Abstract

Thyroid carcinoma is the most common endocrine malignancy in dogs. Thyroidectomy and radiation therapy control local disease, yet are not always feasible, and efficacious medical therapies need to be identified. Toceranib phosphate has been reported to provide clinical benefit (CB) in dogs with thyroid carcinoma, while its role in treatment-naïve thyroid tumours has not been well-described. The objective of this study was to describe the use of toceranib in the management of thyroid carcinomas in dogs in both the naïve-disease and prior therapy-settings. A medical record search identified 42 dogs diagnosed with thyroid carcinoma and treated with toceranib, of which 26 and 16 dogs were in settings of naïve-disease and after prior therapy, respectively. Twenty-three (88.4%) and twelve (75%) dogs experienced CB in the naïve and prior therapy settings, respectively. The median [95% confidence interval] progression free interval (PFI) for dogs in the naïve and prior therapy settings were 206 [106,740] and 1015 [92,1015] days, respectively. The median overall survival time (OST) for dogs in the naïve and prior therapy settings were 563 [246,916] and 1082 [289,1894] days, respectively. Overall, the data provided no evidence for differences in overall PFI (P > .20) or OST (P = .15) between settings. However, when asymptomatic at the time of diagnosis, dogs in the naïve setting showed poorer survival prognosis (estimated hazard ratio 17.2 [1.8, 163]) relative to dogs in the prior therapy setting. This study characterizes PFI, OST and CB with minimal AE in dogs with thyroid carcinoma treated with toceranib in both the naïve and prior therapy settings.

WITHDRAWN: Management of canine insulinomas with toceranib phosphate: 30 cases (2009-2019).

“…Although a necropsy was not performed, it is possible that this patient experienced a treatment-associated grade 5 gastrointestinal AE. This case highlights the fact that, while most dogs have only mild to moderate AEs associated with toceranib, it is not without risk [16][17][18][19][20][21][22][23][24][25][26][27]33]. Given that earlier studies evaluating toceranib doses of 2.5 to 3.5 mg/kg found no differences in biologic activity observed at higher doses, it may be reasonable to administer toceranib at a dose between 2.4 and 3.0 mg/kg to avoid severe gastrointestinal toxicity and frequent drug holidays when treating dogs with insulinoma [32,34].…”

“…Moreover, in the initial phase I study for toceranib, as well as subsequent off-label investigations of toceranib, clinical responses were observed in dogs with a spectrum of solid tumour types [18][19][20][21][22][23][24][25][26][27]. More recently, a case report described a dog diagnosed with metastatic insulinoma experiencing long-term glycemic control with toceranib [28].…”

WITHDRAWN: Management of canine insulinomas with toceranib phosphate: 30 cases (2009-2019)

“…Toceranib phosphate (Palladia®; Zoetis Animal Heath, Madison, NJ, USA) is a small molecule inhibitor with similar molecular targets to sunitinib, some of which have been identi ed in two canine tumours of neuroendocrine histology [23][24][25]. Moreover, in the initial phase I study for toceranib, as well as subsequent off-label investigations of toceranib, clinical responses were observed in dogs with a spectrum of solid tumour types [26][27][28][29][30][31][32][33][34][35][36]. More recently, a case report described a dog diagnosed with metastatic insulinoma experiencing long-term glycemic control with toceranib [37].…”

Retrospective evaluation of toceranib phosphate (Palladia) for treatment of different tumor types in 31 dogs

“…There have been few studies of the relation-ship between tumor type and prognosis, but our study shows that epithelial tumors have a low recurrence rate and a high survival rate. In the previous studies assessing toceranib, clinical benefits have mainly been shown in epithelial tumors ('-carcinoma') and MCTs [1,6,10,11,13,14,18]. Conversely, few studies have reported effects on mesenchymal tumors such as GIST, OSA, injection site sarcoma, and histiocytic sarcoma, and these studies were limited by small populations [11,18,[23][24][25].…”

“…Various reports have described the evaluation of toceranib [7,8]. Apart from MCTs [6,9], off-label uses have been described in a variety of tumors, including those of epithelial origin (apocrine gland anal sac adenocarcinoma [AGASA] [10,11], squamous cell carcinoma [SCC] [12], hepatocellular carcinoma [13], nasal carcinoma [11], thyroid carcinoma [14], and mammary gland tumor [15]), mesenchymal origin (osteosarcoma [OSA] [11,16,17], gastrointestinal stromal tumor [GIST] [18], and melanoma [5]), and round cell origin (lymphoma [19]). In one study that reported toceranib's use in the treatment of solid tumors (AGASA, OSAs, thyroid carcinoma, and head and neck carcinoma), a clinical benefit was observed in 63/85 (74.1%) dogs [11].…”