toceranib-phosphate and Adenocarcinoma

An 11-year-old neutered male Miniature Poodle with a stage 3 apocrine gland adenocarcinoma was started on chemotherapy with toceranib phosphate after surgery. Beginning on day 10 of toceranib, the dog's foot pads became erythematous and hyperkeratinized. The dog complained of pain, inability to walk, depression, and loss of appetite. The symptoms resolved when toceranib was discontinued and reappeared when toceranib was resumed. Grade 3 palmar-plantar erythrodysesthesia was identified as an adverse event of toceranib based on the VCOG-CTCAE and Naranjo scale. Although very rare in veterinary medicine, clinicians should consider that palmar-plantar erythrodysesthesia can occur after toceranib administration.

Topics: Adenocarcinoma; Anal Sacs; Animals; Apocrine Glands; Dog Diseases; Dogs; Male; Pyrroles

Canine pancreatic carcinoma is a rare, aggressive tumour that is often diagnosed late in the course of disease. Effective treatment strategies have been elusive, and overall survival time is short. In humans, treatment with tyrosine kinase inhibitors alone, or in combination with IV gemcitabine, have been moderately effective. As canine and human pancreatic carcinomas share many clinical aspects, strategies that mimic human treatment regimens may confer a better outcome in canine patients. The aim of this study was to assess the role of the veterinary tyrosine kinase inhibitor, toceranib phosphate, in the treatment of cytologically or histologically confirmed canine pancreatic carcinomas.. Retrospectively, medical records of dogs with confirmed pancreatic carcinoma treated with toceranib were reviewed. Eight dogs were identified that fit the inclusion criteria. Toceranib was well-tolerated by all patients. Six were treated in the gross disease setting. Four had image-based evaluation of clinical benefit (complete response, partial response, or stable disease of > 10 weeks). Of those patients, 1 achieved a partial response, 2 stable disease, and 1 had progressive disease, for an overall clinical benefit rate of 75 %. An additional dog had clinically stable disease that was not confirmed via imaging. The toceranib-specific median overall survival time was 89.5 days (range: 14-506 days).. Although limited in patient number, this small study suggests that toceranib may have biologic activity in dogs with pancreatic carcinoma. Larger, prospective studies are needed to confirm these preliminary results and define the use of toceranib in the microscopic disease setting.

Topics: Adenocarcinoma; Animals; Antineoplastic Agents; Dog Diseases; Dogs; Female; Indoles; Male; Pancreatic Neoplasms; Pyrroles; Retrospective Studies

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

Toceranib phosphate (TOC) could be made widely available for treating tumors in dogs if evidence shows that TOC inhibits recurrence after surgery.. To investigate how postoperative adjuvant treatment with TOC modulates the tumor microenvironment (TME), by assessing effects on angiogenic activity, tumor-infiltrating regulatory T cells (Tregs), and intratumoral hypoxia.. Ninety-two client-owned dogs were included: 28 with apocrine gland anal sac adenocarcinoma, 24 with small intestinal adenocarcinoma, 22 with lung adenocarcinoma, and 18 with renal cell carcinoma.. Retrospective, multicenter study comparing time to progression (TTP) between 42 dogs treated by surgery and TOC and 50 dogs treated by surgery alone. Differences were analyzed in the expression of vascular endothelial growth factor receptor-2 (VEGFR2) and the number of Foxp3. Median TTP for dogs treated by surgery and TOC (360 days) was higher than that for dogs treated by surgery alone (298 days; hazard ratio, 0.82; 95% confidence interval [CI], 0.65-0.96; P = .02). In dogs treated by surgery and TOC, VEGFR2 expression and the number of Tregs and HIF-1α. Toceranib phosphate could prove to be a useful postoperative adjuvant treatment because of its modulation of the TME.

Topics: Adenocarcinoma; Animals; Carcinoma, Renal Cell; Chemotherapy, Adjuvant; Dog Diseases; Dogs; Female; Indoles; Male; Neoplasm Recurrence, Local; Neoplasms; Pyrroles; Retrospective Studies; Treatment Outcome; Tumor Microenvironment; Vascular Endothelial Growth Factor Receptor-2

To assess response and outcome in dogs with stage 4 anal sac apocrine gland adenocarcinoma (ASAGA) treated with toceranib phosphate as the sole chemotherapeutic agent.. Retrospective case series.. 15 client-owned dogs with stage 4 ASAGA treated with toceranib phosphate between March 2013 and June 2017.. Medical records were reviewed, and data collected included signalment, clinical signs, results of physical examinations and diagnostic procedures, treatments, response, follow-up information, and outcomes. Adverse events and response to treatment were assessed according to standard guidelines, and the Kaplan-Meier product limit method was used for analyses of progression-free interval and survival time.. No dogs had a complete or partial response to treatment with toceranib; however, 13 dogs had signs of clinical benefit. No dogs had signs of toxic effects related to toceranib or were withdrawn completely from treatment because of adverse events. Median progression-free interval and median survival time were 354 and 356 days, respectively.. Results of the present study indicated that dogs with stage 4 ASAGA treated with toceranib had improved outcomes, compared with outcomes previously reported for dogs with ASAGA that had received non-tyrosine kinase inhibitor treatments. Some dogs had improvement in clinical signs, but euthanasia was often performed because of signs of locoregional failure; therefore, toceranib alone may not be an appropriate treatment for dogs with marked clinical signs attributed to ASAGA, particularly when signs suggest limited quality of life. Further study of toceranib in multimodality treatments for dogs with advanced ASAGA is warranted.

Topics: Adenocarcinoma; Anal Sacs; Animals; Apocrine Glands; Dog Diseases; Dogs; Indoles; Pyrroles; Quality of Life; Retrospective Studies; Treatment Outcome

A 12-year-old, male miniature dachshund has an ulcer on the footpad of the right hind limb. Despite treatment for longer than 6 months, the ulcer did not heal. Biopsy of the lesion was done to make a definitive diagnosis. Histologically, there were lumens containing weakly eosinophilic fluid surrounded by tumor cells with a similar circular pale nucleus and distinct nucleoli that showed some variation in size. Immunohistochemically, the tumor cells were positive for cytokeratin (AE1/AE3) and vimentin, were negative for S100 and p63. A poorly differentiated eccrine adenocarcinoma was diagnosed. Treatment was started with toceranib, an anti-angiogenic agent, and enlargement of the lesion was not observed during the administration period.

Topics: Adenocarcinoma; Angiogenesis Inhibitors; Animals; Biopsy; Dog Diseases; Dogs; Hindlimb; Immunohistochemistry; Indoles; Keratins; Male; Pyrroles; Sweat Gland Neoplasms; Vimentin

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