toceranib-phosphate and Cat-Diseases

Recent advances in molecular biology have permitted the identification and characterization of specific abnormalities regarding cell signaling and function in cancer cells. Proteins that are found to be dysregulated in cancer cells can serve as relevant targets for therapeutic intervention. Although there are several approaches to block proteins that contribute to cellular dysfunction, the one most commonly used involves a class of therapeutics called small molecule inhibitors. Such inhibitors work by disrupting critical pathways/processes in cancer cells, thereby preventing their ability to grow and survive.

Topics: Animals; Benzamides; Cat Diseases; Cats; Dog Diseases; Dogs; Indoles; Neoplasms; Piperidines; Protein Kinase Inhibitors; Pyridines; Pyrroles; Thiazoles

Non-steroidal anti-inflammatory drugs (NSAIDs) are infrequently utilized in cats due to concern for renal compromise; however, recent studies demonstrate tolerability of low dose meloxicam. Toceranib phosphate is used to treat several feline cancers and is well tolerated. This study aimed to determine the tolerability and adverse event profile of combined toceranib and low dose meloxicam in cancer-bearing cats. Secondary goals involved assessing anticancer tumor efficacy and impact upon quality of life and analgesia.. Cats with any cancer not involving the kidneys were eligible. The study adopted a conventional 3 + 3 dose escalation design. Toceranib was administered every other day at a standard dose with meloxicam administered in an escalating fashion in subsequent cohorts, at a starting dose of 0.01 mg/kg on opposite days to toceranib, up to a maximum of 0.02 mg/kg daily, based upon previous safety studies. Laboratory work, blood pressure, tumor measurements, pain score and client-completed quality-of-life surveys were recorded every 2-4 weeks during the 12-week study period.. Twenty-one cats were enrolled. When combined with toceranib, a meloxicam dose of 0.02 mg/kg q24h was safe and well tolerated, with no cats being withdrawn due to adverse events from the drug combination. The majority of cats demonstrated clinical benefit with stable to mildly improved tumor measurements, quality of life and pain scores.. Low dose meloxicam combined with toceranib is safe and well tolerated in cancer-bearing cats. Continued patient recruitment and data collection are needed to determine the maximum tolerated dose of meloxicam. The results of our study will guide further phase II/III trials.

Topics: Animals; Cat Diseases; Cats; Meloxicam; Neoplasms; Pain; Quality of Life

Because of their locally invasive growth and high recurrence rate despite of aggressive local therapy, treatment of feline sarcomas is challenging. The tyrosine kinase inhibitor (TKI) toceranib is currently licensed for the treatment of canine mast cell tumours. There are only few reports about TKI usage in cats. Previous studies indicated promising potential of TKI for the treatment of feline injection site sarcoma (FISS). In this prospective clinical trial, 18 cats with unresectable FISS were treated at a target dosage of 3.25 mg kg

Topics: Animals; Antineoplastic Agents; Cat Diseases; Cats; Female; Indoles; Injections; Male; Protein-Tyrosine Kinases; Pyrroles; Sarcoma; Soft Tissue Neoplasms

To retrospectively assess the biological response in cats with pancreatic carcinoma treated with toceranib phosphate.. Twenty-six client-owned cats.. Patient information from multiple institutions was solicited. Twenty cats were treated for gross disease and 6 for microscopic disease/incomplete margins. Clinical benefit (complete response, partial response, or stable disease ≥ 10 wk) was observed in 9/20 cats treated in the gross disease setting (45%; complete response:. Toceranib phosphate was well-tolerated and provided modest clinical benefit to a subset of cats treated.. Although feline exocrine pancreatic carcinoma continues to be a challenging disease to treat, toceranib phosphate appeared to provide potential clinical benefit.. Évaluation rétrospective de l’utilisation du phosphate de tocéranib (Palladia) dans le traitement du carcinome pancréatique félin.. Évaluer rétrospectivement la réponse biologique chez les chats atteints d’un carcinome pancréatique traités par le phosphate de tocéranib.. Vingt-six chats appartenant à des clients.. Les informations sur les patients de plusieurs institutions ont été sollicitées via une enquête REDCap envoyée par courriel. Pour être inclus, les chats devaient avoir un diagnostic confirmé de carcinome pancréatique exocrine, soit par histopathologie, soit par cytologie, soit par les deux; avoir reçu un traitement par phosphate de tocéranib; et disposer de données de suivi adéquates pour l’analyse.. Vingt chats ont été traités pour une maladie macroscopique et six pour une maladie microscopique/marges incomplètes. Un bénéfice clinique (réponse complète, réponse partielle ou maladie stable ≥ 10 semaines) a été observé chez 9 chats sur 20 traités dans le cadre d’une maladie macroscopique (45 %; réponse complète:. Le phosphate de tocéranib a été bien toléré et a apporté un bénéfice clinique modeste à un sous-ensemble de chats traités.. Bien que le carcinome pancréatique exocrine félin continue d’être une maladie difficile à traiter, le phosphate de tocéranib semble offrir un bénéfice clinique potentiel.(Traduit par D

Topics: Animals; Antineoplastic Agents; Cat Diseases; Cats; Humans; Indoles; Pancreatic Neoplasms; Retrospective Studies

A fifteen-year old, female spayed domestic longhaired cat was presented for a routine vaccination during which an incidental abdominal mass was palpated. After further inquiry, occasional vomiting was reported to occur once every few weeks to months, associated with no other gastrointestinal signs.. Ultrasonography revealed a gastric mass. Histopathology and immunohistochemistry confirmed a CD117 positive, smooth muscle actin and desmin negative neoplasm, consistent with a gastrointestinal stromal cell tumour (GIST). Treatment was initiated with toceranib phosphate resulting in stable disease for over eighteen months, and the patient was still alive at the time of writing.. GISTs are rare in cats and this is the first report of medical management of feline GIST using toceranib.

Topics: Animals; Cat Diseases; Cats; Female; Gastrointestinal Stromal Tumors; Indoles; Pyrroles; Stromal Cells

Objectives The purpose of this study was to solicit and compile data from practicing veterinary specialists regarding their use of toceranib in cats with mast cell neoplasia and to provide initial assessment of possible clinical benefit and adverse events. Methods The American College of Veterinary Internal Medicine and Oncology listservs were used to solicit data pertaining to cases in which toceranib was used in the treatment of feline mast cell neoplasia. Cases were included if the following data were received: signalment (age, sex, breed), diagnosis of mast cell neoplasia by either cytology or histopathology, anatomic classification of disease (cutaneous, splenic/hepatic, gastrointestinal, other), previous and concurrent treatment, toceranib dose (mg/kg) and schedule, duration of therapy, best response and documentation of adverse events. Results Case data from 50 cats with cutaneous (n = 22), splenic/hepatic (visceral) (n = 10), gastrointestinal (n = 17) or other (n = 1) mast cell neoplasia were received. Clinical benefit was seen in 80% (40/50), including 86% (19/22) with cutaneous, 80% (8/10) with visceral and 76% (13/17) with gastrointestinal involvement. A majority of cats (n = 35) received glucocorticoids during toceranib treatment. Median duration of treatment in cats experiencing clinical benefit was 36 weeks (range 4-106 weeks), 48 weeks (range 12-199 weeks) and 23 weeks (range 13-81 weeks) for cutaneous, visceral and gastrointestinal cases, respectively. Toceranib was administered at a median dose of 2.5 mg/kg (range 1.6-3.5 mg/kg); in 90% (45/50) the drug was given three times per week. Treatment was generally well tolerated with 60% (30/50) of cats experiencing adverse events. The majority of these events were low-grade (grade 1 or 2) gastrointestinal or hematologic events that resolved with treatment break and/or dose adjustment. Conclusions and relevance Toceranib appears to be well tolerated in feline patients with mast cell neoplasia. Biologic activity of this drug is evident in the studied cats; however, further prospective studies are needed to elucidate fully its role in treatment of this disease.

Topics: Animals; Antineoplastic Agents; Cat Diseases; Cats; Female; Indoles; Male; Mast Cells; Neoplasms; Pyrroles; Retrospective Studies; Treatment Outcome

An 11-year-old, spayed female, domestic shorthair cat was presented with a non-resectable abdominal mass diagnosed as carcinomatosis of pancreatic origin. Treatment with toceranib phosphate was started. Abdominal ultrasound approximately 1 year after diagnosis revealed progressive disease. The cat was humanely euthanized approximately 792 days after initial presentation due to progressive clinical signs.

Topics: Animals; Antineoplastic Agents; Carcinoma; Cat Diseases; Cats; Female; Indoles; Pancreatic Neoplasms; Pyrroles

Objectives The aim of the study was to determine the clinical benefit and adverse event profile of toceranib phosphate in the treatment of feline oral squamous cell carcinoma (FOSCC). Methods Data obtained from the medical records of cats with oral squamous cell carcinoma diagnosed between 2010 and 2014 treated with toceranib phosphate were compared with medical record data from cats that did not receive toceranib, cytotoxic chemotherapy or radiation, to determine the response to toceranib treatment and adverse event profile of toceranib in cats. Concurrent use of non-steroidal anti-inflammatory drugs (NSAIDs) was allowed. Results Forty-six cats with FOSCC were included; 23 received treatment with toceranib (group 1) and 23 did not (group 2). The overall biological response rate in group 1 was 56.5%. Median survival time of toceranib-treated cats was significantly longer at 123 days compared with 45 days in cats not treated with toceranib ( P = 0.01). Cats achieving stable disease or better on toceranib therapy had significantly longer progression-free survival ( P <0.0001) and median survival ( P = 0.0042) times than those with progressive disease on toceranib. Administration of NSAIDs was also associated with significantly improved survival time ( P = 0.0038) among all cats. Anorexia was common but may reflect the underlying disease in these patients. Toceranib was well tolerated in cats, with the most common side effect being mild gastrointestinal toxicity. Conclusions and relevance Toceranib was well tolerated in cats with oral squamous cell carcinoma and may lead to improved survival times, especially when combined with NSAIDs. NSAID administration was also associated with improved survival times, and the relative benefit of toceranib and NSAIDs is difficult to determine from this retrospective study. Despite improvement in survival times, long-term survival in this patient population remained poor. As toceranib was well tolerated and may improve survival time, prospective evaluation of toceranib alone is warranted to assess response as a single agent and as part of multimodal therapy in an effort to achieve a more durable response in FOSCC.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents; Carcinoma, Squamous Cell; Cat Diseases; Cats; Disease-Free Survival; Female; Indoles; Male; Mouth Neoplasms; Pyrroles; Retrospective Studies; Treatment Outcome

Objectives Squamous cell carcinoma (SCC) is the most common oral tumor in cats and typically carries a poor prognosis with current treatment options. The objective of this study was to evaluate the toxicity of toceranib phosphate (Palladia; Pfizer) in cats with oral SCC in combination with other treatment modalities. Methods In this study, 35 cats were retrospectively evaluated to determine toxicity when treated with toceranib in combination with other treatment modalities. Cats received toceranib at a median dose of 2.75 mg/kg (range 1.9-4.17 mg/kg) 3 days a week. Cats also underwent additional therapies, including surgical excision, radiation therapy, chemotherapy and/or use of non-steroidal anti-inflammatory drugs. Results Toxicity was seen in six cats, with five cases of grade 1 or 2 gastrointestinal (GI) toxicity and one grade 4 metabolic toxicity. Toceranib was discontinued in one cat and two cats received dose reductions. None of the cats required treatment delays or hospitalization due to toxicity. Median toceranib treatment duration was 77 days (range 7-741 days). Conclusions and relevance This study revealed that toceranib was well tolerated by the majority of cats, with five cases of low-grade GI toxicity and one case of metabolic toxicity. Given the favorable toxicity profile, future studies further evaluating the safety and efficacy of toceranib for cats with oral SCC should be considered.

Topics: Animals; Antineoplastic Agents; Carcinoma, Squamous Cell; Cat Diseases; Cats; Combined Modality Therapy; Disease-Free Survival; Female; Indoles; Male; Mouth Neoplasms; Pyrroles; Retrospective Studies; Treatment Outcome; United States

The purpose of this study was to describe the toxicity profile of toceranib phosphate in tumour bearing cats. Medical records were reviewed from seven institutions. Patients with incomplete medical records and those receiving concurrent chemotherapy or NSAIDs (non-steroidal anti-inflammatory) were excluded. Fifty-five cats met the inclusion criteria. Carcinoma was diagnosed in 55% of cases. Median oral toceranib dose was 2.7 mg kg

Topics: Alanine Transaminase; Animals; Antineoplastic Agents; Azotemia; Cat Diseases; Cats; Female; Gastrointestinal Tract; Indoles; Male; Neoplasms; Neutropenia; Pyrroles; Retrospective Studies; Thrombocytopenia

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.

Topics: Animals; Antineoplastic Agents; Carcinoma, Squamous Cell; Cat Diseases; Cats; Cohort Studies; Female; Indoles; Male; Pyrroles; Retrospective Studies; Skin Neoplasms; Treatment Outcome