toceranib-phosphate and Neoplasms

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

Tyrosine kinases (TKs) are key mediators of signalling pathways in cells. Located at the surface of the cell, within the cytoplasm or in the nucleous, TKs have been showed to be involved in regulation of normal cellular processes and also play an important role in the development, progression and spread of several types of cancer. Seventy percent of TK's are Receptor Tyrosine Kinases and these have become key targets for cancer therapy. This short synopsis is intended to give the reader an introduction to this area of targeted therapy for cancer as a prelude to this special edition of Veterinary and Comparative Oncology.

Topics: Animals; Antineoplastic Agents; Benzamides; Drug Therapy, Combination; Humans; Indoles; Neoplasms; Piperidines; Pyridines; Pyrroles; Receptor Protein-Tyrosine Kinases; 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

Topics: Animals; Carboplatin; Dog Diseases; Dogs; Drug Therapy, Combination; Female; Indoles; Male; Neoplasms; Pyrroles

Topics: Animals; Antibiotics, Antineoplastic; Antineoplastic Agents; Dog Diseases; Dogs; Doxorubicin; Drug Administration Schedule; Drug Therapy, Combination; Female; Flow Cytometry; Indoles; Male; Neoplasms; Neutropenia; Pyrroles

While maintaining a standard toceranib dosage [2.75 mg kg(-1) , PO, every other day (EOD)], three dose-escalating CCNU cohorts up to and including 60 mg m(-2) , PO, q3wk, were completed. The dose-limiting toxicities (DLT) for the combination were neutropenia and the maximum tolerated dose (MTD) for CCNU when given with continuous toceranib was determined to be 50 mg m(-2) , q3wk. While activity is not a primary objective of phase I trials, we observed one complete (lymphoma) and four partial responses (lymphoma, sarcoma, undifferentiated carcinoma and prostatic carcinoma) and two dogs experienced stable disease for >6 weeks [gastric adenocarcinoma and metastatic multilobulated osteochondrosarcoma (MLO)] for an objective response rate of 38.4% and a biological response rate of 53.8%. Concurrent continuous toceranib (2.75 mg kg(-1) , EOD) and pulse dose CCNU (50 mg m(-2) , q3wk) was well tolerated. Phase II effectiveness and phase III prospective randomized trials should further interrogate the potential activity of this combination.

Topics: Animals; Antineoplastic Agents; Dog Diseases; Dogs; Dose-Response Relationship, Drug; Drug Combinations; Indoles; Lomustine; Neoplasms; Pyrroles

Toceranib phosphate and piroxicam have individually demonstrated antineoplastic activity. Additionally, non-steroidal anti-inflammatory therapy is often warranted in aged cancer-bearing dogs for management of osteoarthritis comorbidity. As concurrent use may be warranted for a given individual and the adverse event (AE) profile for each can be overlapping (gastrointestinal), a phase I trial was performed in tumour-bearing (non-mast cell) dogs to establish the safety of the combination using a standard 3+3 cohort design. Five dose-escalating cohorts, up to and including approved label dosage for toceranib and standard dosage for piroxicam, were completed without observing a frequency of dose-limiting AEs necessitating cohort closure. Therefore, the combination of standard dosages of both drugs (toceranib, 3.25 mg kg(-1), every other day; piroxicam, 0.3 mg kg(-1) daily) is generally safe. Several antitumour responses were observed. As with single-agent toceranib, label-indicated treatment holidays and dose reductions (e.g. 2.5-2.75 mg kg(-1)) may occasionally be required owing to gastrointestinal events.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents; Dog Diseases; Dogs; Drug Therapy, Combination; Female; Gastrointestinal Diseases; Indoles; Male; Neoplasms; Piroxicam; Protein-Tyrosine Kinases; Pyrroles

The purpose of the following study was to investigate the safety and efficacy of the novel multitargeted indolinone receptor tyrosine kinase (RTK) inhibitor, SU11654, using a canine model of spontaneous tumors. This p.o. bioavailable compound exhibits potent inhibitory activity against members of the split kinase family of RTKs, including vascular endothelial growth factor receptor, platelet-derived growth factor receptor, Kit, and Flt-3, resulting in both direct antitumor and antiangiogenic activity.. This was a Phase I trial in which successive cohorts of dogs with spontaneous tumors that had failed standard treatment regimens received escalating doses of SU11654 as oral therapy. Pharmacokinetics, toxicity, and tumor response were assessed.. Fifty-seven dogs with a variety of cancers were enrolled; of these, 10 experienced progressive disease within the first 3 weeks. Measurable objective responses were observed in 16 dogs (including 6 complete responses), primarily in mast cell tumors (n = 11), mixed mammary carcinomas (n = 2), soft tissue sarcomas (n = 2), and multiple myeloma (n = 1), for an overall response rate of 28% (16 of 57). Stable disease of sufficient duration to be considered clinically meaningful (>10 weeks) was seen in an additional 15 dogs, for a resultant overall biological activity of 54% (31 of 57).. This study provides the first evidence that p.o. administered kinase inhibitors can exhibit activity against a variety of spontaneous malignancies. Given the similarities of canine and human cancers with regard to tumor biology and the presence of analogous RTK dysregulation, it is likely that such agents will demonstrate comparable antineoplastic activity in people.

Topics: Animals; Antineoplastic Agents; Dog Diseases; Dogs; Dose-Response Relationship, Drug; Enzyme Inhibitors; Female; Indoles; Inhibitory Concentration 50; Male; Models, Chemical; Mutation; Neoplasms; Proto-Oncogene Proteins c-kit; Pyrroles; Receptor Protein-Tyrosine Kinases; Receptors, Vascular Endothelial Growth Factor; Time Factors; Tomography, X-Ray Computed

Receptor tyrosine kinase inhibitors (TKIs) are used to treat human and canine cancers and may be combined with radiation therapy (RT) to enhance tumor control due their anticancer and antiangiogenic effects; however, recent case reports have emerged describing incidences of gastrointestinal toxicity when antiangiogenic therapies are combined with hypofractionated radiotherapy in human cancer patients. We evaluated the incidence of gastrointestinal (GI) toxicity in dogs receiving concurrent hypofractionated abdominal RT and the TKI toceranib (TOC) compared to those receiving abdominal RT alone, TOC alone, or concurrent non-abdominal RT and TOC. Medical records of canine cancer patients were retrospectively reviewed and identified dogs were included in the following treatment categories: dogs which received RT to a portion of the abdomen and concurrent TOC (n = 19), abdominal RT alone (n-29), TOC alone (n = 20), or non-abdominal RT plus TOC (n = 9). Toxicities were graded using the Veterinary Cooperative Oncology Group - Common Terminology Criteria for Adverse Events criteria and compared to published data on TOC-associated GI toxicity. Patients receiving TOC while undergoing abdominal RT had significantly increased rates of any grade of diarrhea (p = 0.002), hyporexia (p = 0.0045), and vomiting (p = 0.003), as well as severe hyporexia (p = 0.003) when compared across the treatment groups. This retrospective study reveals significantly increased incidences of GI toxicity when abdominal RT is combined with TOC in canine patients. These findings are in-line with the clinical concerns reported for increased normal tissue toxicity in human patients when antiangiogenics are combined with RT.

Topics: Abdomen; Animals; Dog Diseases; Dogs; Humans; Incidence; Indoles; Neoplasms; Protein Kinase Inhibitors; Pyrroles; Retrospective Studies

High-grade and metastatic canine mast cell tumors carry a guarded prognosis because of their unpredictable biologic behavior. An ideal chemotherapy regime is yet to be established. The aim of this study was to review the efficacy and toxicity of combination vinblastine and toceranib for high-grade and metastatic mast cell tumors. Twenty-eight dogs were categorized with either high-grade, lymph node metastasis or Stage IV disease. Demographics, disease, and treatment variables were compared between categories (Kruskal-Wallis test for continuous data and Fisher's Exact test for categorical data). Survival times and progression-free intervals (PFI) were calculated and compared between groups (log rank test). The PFI was 310 d [95% confidence interval (CI): 155 to 1425] and overall survival was 373 d (95% CI: 226 to 1219). There was no difference between disease categories for PFI (

Topics: Animals; Dog Diseases; Dogs; Indoles; Mast Cells; Neoplasms; Pyrroles; Retrospective Studies; Vinblastine

Tyrosine kinase inhibitors are widely utilized in veterinary oncology for the treatment of mast cell and solid tumours. In man, these drugs are associated with thyroid dysfunction: however, to date only one study has investigated this in dogs. The aim of this study was to prospectively assess thyroid function in a group of dogs with cancer receiving toceranib. Thirty-four dogs were prospectively enrolled at two referral hospitals into two groups; those receiving toceranib with prednisolone and those receiving toceranib alone. Total thyroxine (TT4) and thyroid stimulating hormone (TSH) was monitored at regular time points during treatment. Follow-up data was available for 19 dogs. Overall, 12 incidences of elevated TSH occurred but none of these dogs had concurrent low TT4 concentrations. There was a significant difference in median TSH at week six compared with baseline. Hypothyroidism was not diagnosed in any patient during the study period. Patient drop-out was higher than anticipated which prevented the assessment of longer term toceranib administration on thyroid function. Toceranib therapy was not associated with hypothyroidism in this study but did result in elevations in TSH which confirms what has been previously reported. Toceranib should be considered to cause thyroid dysfunction in dogs and monitoring is advised.

Topics: Animals; Dog Diseases; Dogs; Female; Hypothyroidism; Indoles; Male; Neoplasms; Prospective Studies; Pyrroles; Thyroid Gland; Thyrotropin; Thyroxine; United Kingdom

In humans, contrast-enhanced CT (CECT) has been used to indirectly assess the antiangiogenic effects demonstrated by a number of tyrosine kinase inhibitors. This retrospective, cross-sectional study aimed to quantitatively evaluate changes in tumor contrast-enhancement (CE) using CECT in solid tumor-bearing dogs treated with toceranib phosphate (TOC). The changes in tumor size and CE were measured using the Hounsfield unit (HU) scale in CECT images before TOC treatment and between 30 and 90 days after initiating the treatment. Among the 36 dogs treated with TOC, eight (22.2%) showed a partial response, 22 (61.1%) showed stable disease, and six (16.7%) showed progressive disease. Thirty (83.3%) of 36 dogs showed a decrease in tumor CE (median: -20%, range: -1% to -48%) after initiating the treatment. The results indicated that tumor CE and size changes were observed in tumor-bearing dogs that were treated with TOC; however, tumor CE was not significantly correlated with tumor regression. We suggest that these results could serve as pilot data to evaluate the antiangiogenic effects associated with TOC.

Topics: Animals; Antineoplastic Agents; Contrast Media; Cross-Sectional Studies; Dog Diseases; Dogs; Female; Humans; Indoles; Male; Neoplasms; Pyrroles; Retrospective Studies; Tomography, X-Ray Computed

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

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

Thyroid dysfunction is associated with the use of tyrosine kinase inhibitors (TKI) in people.. To determine whether dysfunction in the hypothalamic-pituitary-thyroid axis occurs in dogs receiving the TKI, toceranib phosphate.. Forty-three client-owned dogs with cancer.. Prospective, observational study. Concentrations of total thyroxine (TT4), free thyroxine (FT4), total triiodothyronine (TT3), and thyroid-stimulating hormone (TSH) were evaluated on day 0, 30, and 90. Dogs also were evaluated for the presence of thyroglobulin autoantibodies.. The proportion of dogs with low TT4, low FT4, low TT3, high TSH, or primary hypothyroidism (increased TSH and decreased TT4, FT4 or both) did not change over 90 days. Hormone concentrations remained within laboratory reference intervals, but FT4 (P = 0.0032) and TSH (P < 0.0001) changed over time. Mean FT4 was 1.22 ng/dL (95% confidence interval [CI], 1.10-1.34) on day 0 and 1.00 ng/dL (95% CI, 0.86-1.16) on day 90. Mean TSH was 0.17 ng/mL (95% CI, 0.13-0.23) on day 0 and 0.34 ng/mL (95% CI, 0.24-0.48) on day 90. Furthermore, TT4/TT3 ratio also changed over time (P = 0.0086). Mean TT4/TT3 ratio was 2.57 (95% CI, 2.26-2.88) on day 0 and 2.02 on day 90 (95% CI, 1.61-2.44). Thyroglobulin autoantibodies were not detected in any dog.. Toceranib phosphate can disrupt the hypothalamic-pituitary-thyroid axis in dogs. Periodic evaluation of TT4, FT4, TT3, and TSH should be carried out in dogs receiving long-term treatment with this medication.

Topics: Animals; Autoantibodies; Dog Diseases; Dogs; Female; Hypothalamus; Hypothyroidism; Indoles; Male; Neoplasms; Pituitary Gland; Prospective Studies; Pyrroles; Thyroglobulin; Thyroid Gland; Thyrotropin; Thyroxine; Triiodothyronine

The incidence of proteinuria in humans receiving tyrosine kinase inhibitors has been well-documented. Reports of proteinuria with this class of drugs are limited in veterinary medicine. This retrospective study describes the incidence, severity, and progression of proteinuria in 55 dogs treated with toceranib phosphate, with or without concurrent glucocorticoid or NSAID (non-steroidal anti-inflammatory drug). Six dogs were proteinuric at baseline. Twelve of the 49 dogs that were not proteinuric at baseline developed proteinuria while receiving toceranib phosphate. Median urine protein:creatinine (UPC) ratio when proteinuria developed was 0.75 (range: 0.6 to 4.9). There was no association with intermittent glucocorticoid or NSAID use and development of proteinuria (

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents; Dog Diseases; Dogs; Female; Glucocorticoids; Incidence; Indoles; Male; Neoplasms; Proteinuria; Pyrroles; Retrospective Studies

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

Systemic hypertension and proteinuria are established adverse effects of tyrosine kinase inhibitor treatment in people.. The objective of this study was to investigate changes in systolic blood pressure and the incidence of proteinuria secondary to treatment with toceranib phosphate in dogs with cancer.. Twenty-six control dogs and 30 dogs with cancer were evaluated for the first part of the study (baseline characteristics). For the second part (effect of toceranib phosphate treatment), 48 client-owned dogs were evaluated, including 20 control dogs and 28 dogs with various types of neoplasia.. Prospective cohort study. Client-owned healthy control dogs and dogs with cancer were enrolled. Blood pressure and urine protein:creatinine ratios were measured before treatment and 2 weeks after initiation of toceranib phosphate treatment.. Systolic blood pressure was significantly (P = 0.0013) higher in previously normotensive treatment dogs after initiation of treatment with toceranib phosphate (152 mmHg ± 19) compared to baseline (136 mmHg ± 14). 37% of treated dogs developed SBP ≥ 160 mmHg. The prevalence of systemic hypertension (37%) and proteinuria (21%) at baseline in treatment dogs did not differ from that of age-matched healthy controls (15% [P = 0.13] and 0% [P = 0.069], respectively).. Toceranib phosphate treatment might result in increased systolic blood pressures in dogs. Systemic hypertension should be considered a potential adverse effect of this drug in dogs. Systemic hypertension and proteinuria were detected at clinically relevant frequencies in the dogs with cancer before antineoplastic therapies suggesting that monitoring of these variables might be warranted in this population.

Topics: Animals; Antineoplastic Agents; Blood Pressure; Case-Control Studies; Cohort Studies; Dog Diseases; Dogs; Hypertension; Indoles; Neoplasms; Prospective Studies; Protein-Tyrosine Kinases; Proteinuria; Pyrroles

The receptor kinase inhibitor toceranib phosphate (Palladia) was approved for use in dogs in 2009 using a dose of 3.25 mg/kg administered every other day. Preliminary data suggests that lower doses of toeceranib may be associated with a reduced adverse event profile while maintaining sufficient drug exposure to provide biologic activity. The purpose of this study was to determine the Cmax of toceranib in dogs with solid tumors receiving 2.5-2.75 mg/kg every other day and to document the adverse events associated with this dose rate. Secondary objectives included determination of plasma VEGF concentrations in treated dogs and response to therapy.. Dogs with solid tumors were administered toceranib at an intended target dose ranging from 2.5-2.75 mg/kg every other day and plasma samples were obtained for analysis of toceranib and VEGF plasma concentrations on days 0, 7, 14 and 30 of the study at 6 and 8 hours post drug administration. Additionally, plasma samples were obtained at 0, 1, 2, 6, 8, and 12 hours from dogs on day 30 for confirmation of Cmax. Response to therapy was assessed using standard RECIST criteria and adverse events were characterized using the VCOG-CTCAE. Toceranib administered at doses between 2.4-2.9 mg/kg every other day resulted in an average 6-8 hr plasma concentration ranging from 100-120 ng/ml, well above the 40 ng/ml concentration associated with target inhibition. Plasma VEGF concentrations increased significantly over the 30 day treatment period indicating that VEGFR2 inhibition was likely achieved in the majority of dogs. The lower doses of toceranib used in this study were associated with a substantially reduced adverse event profile compared to the established label dose of 3.25 mg/kg EOD.. Doses of toceranib ranging from 2.4-2.9 mg/kg every other day provide drug exposure considered sufficient for target inhibition while resulting in an adverse event profile substantially reduced from that associated with the label dose of toceranib. This lower dose range of toceranib should be considered for future use in dogs with cancer.

Topics: Animals; Antineoplastic Agents; Dog Diseases; Dogs; Dose-Response Relationship, Drug; Female; Indoles; Male; Neoplasms; Pyrroles; Vascular Endothelial Growth Factor A

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

Topics: Animals; Antineoplastic Agents; Benzamides; Breast Neoplasms; Cats; Disease Models, Animal; Dogs; Female; Humans; Imatinib Mesylate; Indoles; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Mast-Cell Sarcoma; Neoplasms; Piperazines; Piperidines; Protein Kinase Inhibitors; Pyridines; Pyrimidines; Pyrroles; Thiazoles; Transcriptome