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Quality of life (QOL) in dogs with cancer is a key consideration in the assessment of cancer treatment options. Despite interest in dietary strategies to improve management of oncology patients, there have been very few clinical studies showing the impact of diet on adverse effects of chemotherapy in dogs. This study was a randomised, controlled, double-blinded, multicenter clinical trial to investigate a high-protein, increased-fibre diet supplemented with omega-3 fatty acids, for dogs with cancer undergoing standard-of-care chemotherapy. Client-owned dogs with newly diagnosed grade 2 or higher mast cell tumours (or non-resectable/incompletely resected tumours) or multicentric lymphoma were randomised to receive the test diet (n = 24) or control diet (n = 21) for 8 weeks. Primary outcomes were QOL assessments, faecal scores, and blood concentrations of C-reactive protein and monocyte chemoattractant protein-1. Of 12 QOL parameters, 10 significantly improved from baseline to Week 8 in the test group compared with one in the control group. However, differences between the two groups were only statistically significant for 'frequency of signs of illness' (P = .009). There were no significant differences in the incidence of any adverse events, including gastrointestinal adverse events or clinically significant differences in laboratory parameters or faecal scores between the two groups. The absence of an observed negative impact of the test diet, combined with the magnitude of QOL improvements associated with the diet, suggest that a larger trial is warranted., (© 2023 John Wiley & Sons Ltd.)

We evaluated the effect of oligo fucoidan (Laminina Japonica) derived from oceanic brown seaweed on the quality of life in dogs with cancer undergoing chemotherapy in a double-blinded case control study. Included in this prospective study were 100 dogs with a confirmed diagnosis of cancer that were being treated with chemotherapy. Dogs were randomly assigned to be treated with oligo fucoidan (treated group; n = 68) or placebo (placebo group; n = 32). Dogs were evaluated every 2-3 weeks for 3 months with a complete blood count (CBC) and serum biochemistry profile, and a complete history and physical examination by blinded clinicians at The Veterinary Cancer Center. The owners of the dogs enrolled in the study were required at each visit to complete a Quality-of-Life Questionnaire specifically designed for cancer-bearing veterinary patients. The owners were also blinded as to whether their dog was receiving oligo fucoidan or placebo. There were no significant differences between the CBC parameters or the serum biochemical parameters of the dogs in the treated and placebo-controlled groups. There was no significant difference in the median quality of life scores between the 2 cohorts, however, when evaluating the individual quality of life metrics, 5 out of the 23 metrics showed statistically significant improvement, and none of the quality-of-life metrics declined in the oligo fucoidan group as compared to the placebo group. All of the dogs that had a positive change in overall quality of life scores were dogs that received oligo fucoidan. There were minimal adverse side effects of giving the oligo fucoidan to dogs. Treatment with oligo fucoidan was safe and improved some of the quality-of-life metrics in dogs who were being treated with chemotherapy for cancer., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Rabacfosadine (RAB, Tanovea-CA1) is a novel chemotherapy agent conditionally approved for the treatment of lymphoma in dogs., Hypothesis/objectives: To determine the efficacy and safety of RAB in dogs with lymphoma., Animals: One hundred and fifty-eight client-owned dogs with naïve or relapsed multicentric lymphoma were prospectively enrolled from January to October 2019., Methods: Dogs were randomized to receive RAB or placebo at a 3 : 1 ratio. Treatment was given every 21 days for up to 5 treatments. Study endpoints included progression-free survival (PFS), overall response rate (ORR) at a given visit, best overall response rate (BORR), and percent progression free 1 month after treatment completion. Safety data were also collected., Results: The median PFS was significantly longer in the RAB group compared to placebo (82 vs 21 days; P < .0001, HR 6.265 [95% CI 3.947-9.945]). The BORR for RAB-treated dogs was 73.2% (50.9% complete response [CR], 22.3% partial response [PR]) and 5.6% (0% CR, 5.6% PR) for placebo-treated dogs (P < .0001). One month after the last treatment, 37 RAB-treated dogs (33%) were progression free compared with no placebo-treated dogs (P < .0001). The most common adverse events observed in the RAB group were diarrhea (87.5%), decreased appetite (68.3%), and vomiting (68.3%) and were generally low grade and reversible. Serious adverse events were reported in 24 RAB-treated (20%) and 5 placebo-treated dogs (13%)., Conclusions and Clinical Importance: Rabacfosadine demonstrated statistically significant antitumor efficacy in dogs with lymphoma when administered every 21 days for up to 5 treatments as compared to placebo., (© 2021 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC. on behalf of the American College of Veterinary Internal Medicine.)

Background: Rabacfosadine (RAB), a novel antineoplastic agent conditionally licensed for the treatment of lymphoma in dogs, is efficacious in both naïve and previously treated dogs. Its use in combination with L-asparaginase (L-ASP) has not been studied., Hypothesis/objectives: To evaluate the safety and efficacy of L-ASP given concurrently with RAB in dogs with relapsed multicentric lymphoma., Animals: Fifty-two dogs with relapse of lymphoma after treatment with at least 1 doxorubicin-based chemotherapy protocol., Methods: Open-label, multicenter, prospective single-arm clinical trial. Dogs were treated with RAB at 1.0 mg/kg IV every 21 days for up to a total of 5 doses. L-asparaginase was administered at 400 IU/kg SQ concurrently with the first 2 treatments of RAB., Results: The overall response rate (ORR) for all dogs was 67%, with 19 dogs (41%) achieving a complete response (CR). The median progression-free survival time (MPFS) was 63 days (range 5-428 days). Dogs experiencing a CR as their best response had an MPFS of 144 days (range 44-428 days). Adverse events were similar to previous studies evaluating single agent RAB. Failure to achieve a CR and having previously received L-ASP were negative prognostic factors on multivariate analysis., Conclusions and Clinical Importance: Concurrent RAB/L-ASP appears to be both efficacious and safe for treating relapsed multicentric lymphoma in dogs. Adverse events were most often mild and no unexpected toxicoses were observed., (© 2020 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

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.

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.

Background: Standard of care treatment for multicentric lymphoma in dogs remains doxorubicin (DOX)-based combination chemotherapy, but owners may hesitate to commit the time and financial resources to complete such a protocol, typically requiring 12-16 visits. Rabacfosadine (RAB), a double prodrug of the nucleotide analog 9-(2-phosphonylmethoxyethyl) guanine, has substantial single-agent activity in dogs with lymphoma, and a different mechanism of action than DOX., Hypothesis/objectives: Our objective was to evaluate the efficacy and adverse effect (AE) profile of alternating doses of RAB and DOX in dogs with naïve multicentric lymphoma., Animals: Fifty-four dogs with previously untreated lymphoma., Methods: Open-label, multicenter prospective clinical trial. Dogs received alternating RAB (1.0 mg/kg IV weeks 0, 6, 12) and DOX (30 mg/m 2 IV weeks 3, 9, 15). Dogs that achieved complete response (CR) were followed by monthly evaluations. Complete clinicopathological evaluation and assessment of remission and AEs were performed every 21 days., Results: The overall response rate was 84% (68%; CR; 16%; partial response [PR)]. The overall median progression-free interval (PFI) was 194 days (216 for CR and 63 for PR). Most AEs were mild and self-limiting: gastrointestinal and hematologic AEs were most common. Thirteen dogs experienced dermatologic AEs, and 2 dogs developed grade 5 pulmonary fibrosis., Conclusions and Clinical Importance: Alternating RAB/DOX generally was well tolerated and resulted in PFIs comparable to standard DOX-based multi-agent protocols, with fewer treatment visits. Most adverse events were mild or moderate and self-limiting. Further studies are warranted to explore long-term outcome and other RAB chemotherapy combinations., (Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Melanoma is the most common oral malignancy in dogs. This retrospective study evaluated adjuvant carboplatin chemotherapy (with or without radiation therapy) in 17 dogs with malignant oral melanoma following surgical resection. The median dosage and number of doses of carboplatin administered to the 17 dogs was 300 mg m(-2) (range, 150-300 mg m(-2)) and 4 (range, 2-11), respectively. The overall median progression-free survival for all dogs was 259 days [95% confidence interval (CI95), 119-399 days]. The first progression-free survival event was local recurrence in seven dogs (41%) and metastases in seven dogs (41%). The median overall survival for all dogs was 440 days (CI95, 247-633 days). The tumour was the cause of death in 10 dogs (59%). On the basis of this study, systemic therapy with carboplatin may be an appropriate adjunct to local treatment for canine malignant melanoma, although future prospective controlled studies are needed to compare treatment modalities for this aggressive neoplasia., (© 2012 John Wiley & Sons Ltd.)

Thirty-four cases were reviewed in this retrospective study for information on clinical presentation, prognostic indicators, survival time and response to various therapies. The most common presenting clinical signs were weight loss, decreased appetite, vomiting, palpable abdominal mass and diarrhoea. Metastatic disease was confirmed in 11 cats. The overall median survival was 97 days. The median survival times for patients who received chemotherapy or had their masses surgically removed was 165 days. Those patients who had an abdominal effusion present at the time of diagnosis survived a median of 30 days. Cats that received non-steroidal anti-inflammatory drug therapy had a median survival of 26 days. This study confirms that exocrine pancreatic carcinoma in cats is an aggressive tumour with a high metastatic rate and poor prognosis, although three patients survived over 1 year. Fifteen percent of the patients were diabetic, which raises the question as to what the link between diabetes and pancreatic cancer in people and cats may be., (© 2012 John Wiley & Sons Ltd.)

The goal of this study was to determine the efficacy and tolerability of gemcitabine in dogs diagnosed with hepatocellular carcinoma (HCC). Eighteen dogs were examined retrospectively (4 massive HCC, 10 nodular HCC and 4 diffuse HCC). All dogs received gemcitabine at 350-400 mg m(-2) weekly for 5 weeks. Toxicity was graded using VCOG-CTCAE guidelines and response was monitored with serial abdominal ultrasounds. Fifteen dogs completed all five cycles. Toxicity was minimal and consisted of grade I/II vomiting, anorexia and diarrhoea and two episodes of grade III neutropenia. Median survival time for all dogs was 983 days. Median progression free interval was 971 days. Based on the results of this study, surgery remains the best treatment for HCC, despite incomplete resection. There was no improvement in the survival of those diagnosed with nonresectable HCC treated with gemcitabine chemotherapy., (© 2011 Blackwell Publishing Ltd.)

Cancer cells and their associated tumors have long been considered to exhibit unregulated proliferation or growth. However, a substantial body of evidence indicates that tumor growth is subject to both positive and negative regulatory controls. Here, we describe a novel property of tumor growth regulation that is neither species nor tumor-type specific. This property, functionally a type of feedback control, is triggered by the encapsulation of neoplastic cells in a growth-restricting hydrogel composed of an agarose matrix with a second coating of agarose to form 6- to 8-mm diameter macrobeads. In a mouse cell model of renal adenocarcinoma (RENCA cells), this process resulted in selection for a stem cell-like subpopulation which together with at least one other cell subpopulation drove colony formation in the macrobeads. Cells in these colonies produced diffusible substances that markedly inhibited in vitro and in vivo proliferation of epithelial-derived tumor cells outside the macrobeads. RENCA cells in monolayer culture that were exposed to RENCA macrobead-conditioned media exhibited cell-cycle accumulation in S phase due to activation of a G(2)/M checkpoint. At least 10 proteins with known tumor suppression functions were identified by analysis of RENCA macrobead-conditioned media, the properties of which offer opportunities to further dissect the molecular basis for tumor growth control. More generally, macrobead culture may permit the isolation of cancer stem cells and other cells of the stem cell niche, perhaps providing strategies to define more effective biologically based clinical approaches to treat neoplastic disease.

The purpose of this study was to evaluate the efficacy of adding mitoxantrone to a cyclophosphamide, doxorubicin, vincristine, L-asparaginase and prednisone containing protocol. Sixty-five dogs with multicentric lymphoma were evaluated for overall remission and survival times. Remission and survival time versus stage, substage, pretreatment hypercalcaemia and pretreatment steroid administration were also evaluated. Overall median remission for dogs with multicentric lymphoma was 302 days and overall median survival was 622 days. Of the dogs with multicentric lymphoma, 23 (35%) received all scheduled mitoxantrone doses. Only median survival versus substage was found to be significant (substage a median survival was 679 days and substage b median survival was 302 days, P = 0.025). Increasing the total combined dose of doxorubicin and mitoxantrone may improve remission times when compared with historical controls, and further studies are needed to determine how best to utilize mitoxantrone in multidrug chemotherapy protocols for canine multicentric lymphoma.

Background: Dogs with multicentric lymphoma are treated with various cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-based chemotherapy protocols with variable success., Objectives: To describe the progression-free survival (PFS) time and overall survival time (OST) of dogs with T-cell lymphoma or hypercalcemic lymphoma treated with L-asparaginase and mechlorethamine, vincristine, prednisone, procarbazine (MOPP)., Animals: Fifty dogs with T-cell lymphoma, hypercalcemic lymphoma, or both treated at 3 referral veterinary hospitals., Methods: Retrospective study. Case were selected based on histologic or cytologic diagnosis of lymphoma; presence of the T-cell phenotype, presence of hypercalcemia or both; and absence of previous chemotherapy. The T-cell phenotype was determined by flow cytometry, immunocytochemistry, immunohistochemistry, or polymerase chain reaction of antigen receptor rearrangement., Results: The overall response rate was 98% (78% complete response, 20% partial response). The median PFS for the entire study population was 189 days with 25% PFS at 939 days. The median OST for the entire study population was 270 days with 25% surviving 939 days. Twenty percent of the dogs required hospitalization for treatment related complications., Conclusions and Clinical Importance: L-Asp/MOPP chemotherapy might result in longer PFS and OST for dogs with multicentric T-cell lymphoma, dogs with hypercalcemic lymphoma or both, than achieved with CHOP.

A phase I clinical trial evaluating the toxicity of orally-administered imatinib mesylate was performed in 9 tumor-bearing cats. Imatinib is a small molecule, tyrosine kinase inhibitor, which selectively blocks the function of overexpressed proteins associated with various malignancies. Cats included in the study had diagnoses of fibrosarcoma, squamous cell carcinoma, and mast cell tumor, and each cat was staged using CBC and serum biochemistry; urinalysis, thoracic radiographs, and abdominal ultrasonography were performed in some cats. Most cats were treated previously by surgery, radiation therapy, chemotherapy, or some combination of these treatments. None of the cats received any concurrent chemotherapy. Six cats were treated with imatinib mesylate at 1-2 mg/kg PO q24h. Dose escalations were made to 2, 4, and 10 mg/kg PO q24h in 5 cats. Two cats started therapy at 10 mg/kg PO q24h, and 1 cat started therapy at 15 mg/kg PO q24h; all 3 cats remained at these dosages. No signs of toxicity, as evaluated by CBC and serum biochemistry, were noted in 8 of the 9 cats, and minimal gastrointestinal toxicity was observed. Due to the low frequency of adverse effects, further evaluation of imatinib is ongoing at a dosage of 10 mg/kg PO q24h.

Acquired amegakaryocytic thrombocytopenla was diagnosed in four dogs. Initial platelet counts in all four dogs were less than 50,000 x 10(9)/litre and initial bone marrow examinations revealed megakaryocytic hypoplasia with minimal changes in the erythroid and myeloid cell lines. Two dogs had evidence of idiopathic immune-mediated disease and two dogs had evidence of associated infectious disease. One dog had a positive antibody titre to Borrella burgdorferi, and one dog had positive titres to both Ehrlichia canis and B. burgdorferi. Treatment consisted of prednisone and cyclophosphamide for the dogs with presumptive immune-mediated disease, and prednisone and tetracycline for the dogs with positive antibody titres to the Infectious organisms. Both dogs with evidence of associated infectious disease responded to treatment. A postmortem examination did not reveal the underlying aetiology in the two dogs with presumptive idiopathic immune-mediated disease.

A retrospective review over a 5-year period was performed to identify clinical characteristic features and survival in 14 dogs with intestinal leiomyosarcoma after surgery. Anemia, hypoglycemia, polyuria, and polydipsia were identified as common clinical signs in these dogs. Dogs that survived the immediate postoperative period had a median survival of 21.3 months, (range 0.1-72.5 months). The 1- and 2-year survival rates were 75 and 66%, respectively. Dogs with intestinal leiomyosarcoma that survive the immediate postoperative period can experience long-term survival after surgical excision. Furthermore, dogs with histologically documented metastasis at the time of surgery also appear to have a long survival, with a mean survival of 21.7 months (range 4.2-41.5 months).

Nephrogenic diabetes insipidus is caused by an inability of the kidney to concentrate urine despite adequate concentration of vasopressin in blood and is characterized by polyuria, polydipsia, and hyposthenuria in the presence of plasma hyperosmolality. Nephrogenic diabetes insipidus is the result of defects in water homeostasis in the kidney. Nephrogenic diabetes insipidus occurs when the kidneys cannot or do not respond to vasopressin. There are 2 categories of nephrogenic diabetes insipidus. Congenital nephrogenic diabetes insipidus is a rare, inherited, irreversible cause of polyuria and polydipsia in humans that is even rarer in animals. Acquired nephrogenic diabetes insipidus is more common and is often secondary to illness or medication that interferes with the action of vasopressin in the renal tubules. Unlike congenital nephrogenic diabetes insipidus, acquired or secondary nephrogenic diabetes insipidus is often reversible with correction of the associated or causative problem.

Malignant neuroendocrine carcinoma of the skin (Merkel cell tumor) was diagnosed in an 18-year-old spayed female Maine Coon Cat. The diagnosis was made on the basis of morphologic and electron microscopic findings. The cat was euthanatized 321 days after surgical excision of the tumor. The tumor's malignancy contrasted with the benign nature of Merkel cell tumors reported in dogs and was consistent with the malignancy of Merkel cell tumors reported in humans.

Nephrogenic diabetes insipidus was diagnosed in a dog with an intestinal leiomyosarcoma. The diagnosis of nephrogenic diabetes insipidus was made on the basis of results of serum biochemical tests, urinalyses, and a water-deprivation test, along with a lack of response to exogenous administration of vasopressin following the water-deprivation test. The temporal association between resection of the intestinal mass and resolution of clinical signs of diabetes insipidus (i.e., polyuria and polydipsia) and between recurrence of clinical signs and detection of metastatic disease suggests that there may have been a causal relationship, and nephrogenic diabetes insipidus may have developed as a paraneoplastic syndrome in this dog.