toceranib-phosphate and Anal-Gland-Neoplasms

There is no widely accepted standard medical treatment for apocrine gland anal sac adenocarcinoma (AGASACA) in dogs. Targeted agents such as toceranib may be effective in treatment of AGASACA, but the number of clinical reports investigating its efficacy is limited.. To evaluate the efficacy of toceranib treatment of AGASACA in dogs, and to assess prognostic factors in the study population. Our hypothesis was that toceranib would provide a clinical benefit in the treatment of dogs with AGASACA.. Thirty-six client-owned dogs with either a cytologic or histologic diagnosis of AGASACA that were treated with toceranib alone or in combination with surgery, nonconcurrent chemotherapy or both.. Retrospective study.. The median progression-free survival (PFS) and overall survival time (OST) for the study population was 313 days and 827 days, respectively. A clinical benefit from toceranib treatment was observed in 69% of dogs, with 20.7% of dogs experiencing partial response and 48.3% of dogs experiencing stable disease. Dogs that responded to toceranib treatment had significantly prolonged PFS and OST. Hypercalcemia was a negative prognostic factor for clinical outcomes.. Toceranib is effective in the treatment of AGASACA in dogs. Prospective, controlled clinical trials are needed to determine the efficacy of toceranib in comparison to other treatment protocols for dogs with AGASACA.

Topics: Adenocarcinoma; Anal Gland Neoplasms; Anal Sacs; Animals; Apocrine Glands; Disease-Free Survival; Dog Diseases; Dogs; Female; Indoles; Male; Pyrroles; Retrospective Studies; Treatment Outcome; Wisconsin

The purpose of this study was to provide an initial assessment of the potential biologic activity of toceranib phosphate (Palladia®, Pfizer Animal Health, Madison, NJ, USA) in select solid tumours in dogs. Cases in which toceranib was used to treat dogs with apocrine gland anal sac adenocarcinoma (AGASACA), metastatic osteosarcoma (OSA), thyroid carcinoma, head and neck carcinoma and nasal carcinoma were included. Clinical benefit (CB) was observed in 63/85 (74%) dogs including 28/32 AGASACA [8 partial response (PR), 20 stable disease (SD)], 11/23 OSAs (1 PR and 10 SD), 12/15 thyroid carcinomas (4 PR and 8 SD), 7/8 head and neck carcinomas [1 complete response (CR), 5 PR and 1 SD] and 5/7 (1 CR and 4 SD) nasal carcinomas. For dogs experiencing CB, the median dose of toceranib was 2.8 mg kg(-1) , 36/63 (58.7%) were dosed on a Monday/Wednesday/Friday basis and 47/63 (74.6%) were treated 4 months or longer. Although these data provide preliminary evidence that toceranib exhibits CB in dogs with certain solid tumours, future prospective studies are necessary to define its true activity.

Topics: Adenocarcinoma; Anal Gland Neoplasms; Anal Sacs; Animals; Antineoplastic Agents; Apocrine Glands; Bone Neoplasms; Carcinoma; Dog Diseases; Dogs; Female; Head and Neck Neoplasms; Indoles; Male; Neoplasms; Nose Neoplasms; Osteosarcoma; Pyrroles; Receptor Protein-Tyrosine Kinases; Skin Neoplasms; Thyroid Neoplasms

Toceranib phosphate (Palladia) has a reported objective response rate of 25% in both canine apocrine gland anal sac adenocarcinoma (AGASACA) and thyroid carcinoma (TC), with stable disease occurring in an additional 50-60% of dogs. The basis for the observed responses to toceranib is not known. The purpose of this study was to evaluate AGASACA and TC samples for the expression and activation of VEGFR2, PDGFRα, PDGFRβ, KIT and RET to assess whether dysregulation of these receptor tyrosine kinases (RTKs) may contribute to the biologic activity of toceranib.. mRNA for VEGFR2, PDGFRα/β, KIT and RET was detected in all AGASACA samples. mRNA for VEGFR2, PDGFRα/β, and KIT was detected in all TC samples, while mRNA for RET was amplified in 10/15 samples. No phosphorylation of VEGFR2, PDGFRα/β, or KIT was observed on the arrays. However, phosphorylation of RET was detected in 54% of the primary AGASACA and 20% of TC. VEGFR2 was expressed in 19/24 primary and 6/10 metastatic AGASACA and 6/15 TC samples. KIT was present in 8/24 primary and 3/10 metastatic AGASACA and 9/15 TC samples. PDGFRα expression was noted in all tumor samples. In contrast PDGFRβ expression was found in only a few tumor samples but was evident in the stroma of all tumor specimens.. Known targets of toceranib are expressed in both AGASAC and TC. Given the observed expression of VEGFR and PDGFRα/β and phosphorylation of RET, these RTKs merit investigation as to their roles in the biology of AGSACA and TC and their contribution to toceranib's activity.

Topics: Anal Gland Neoplasms; Anal Sacs; Animals; Carcinoma; Dog Diseases; Dogs; Female; Gene Expression Regulation, Neoplastic; Indoles; Male; Proto-Oncogene Proteins c-kit; Proto-Oncogene Proteins c-ret; Pyrroles; Receptors, Platelet-Derived Growth Factor; RNA, Messenger; Thyroid Neoplasms; Vascular Endothelial Growth Factor Receptor-2