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.
Naturally occurring canine cancers have remarkable similarities to their human counterparts. To better understand these similarities, we investigated 671 client-owned dogs from 96 breeds with 23 ...common tumor types, including those whose mutation profile are unknown (anal sac carcinoma and neuroendocrine carcinoma) or understudied (thyroid carcinoma, soft tissue sarcoma and hepatocellular carcinoma). We discovered mutations in 50 well-established oncogenes and tumor suppressors, and compared them to those reported in human cancers. As in human cancer, TP53 is the most commonly mutated gene, detected in 22.5% of canine tumors overall. Canine tumors share mutational hotspots with human tumors in oncogenes including PIK3CA, KRAS, NRAS, BRAF, KIT and EGFR. Hotspot mutations with significant association to tumor type include NRAS G61R and PIK3CA H1047R in hemangiosarcoma, ERBB2 V659E in pulmonary carcinoma, and BRAF V588E (equivalent of V600E in humans) in urothelial carcinoma. Our findings better position canines as a translational model of human cancer to investigate a wide spectrum of targeted therapies.
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.
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.
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.
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.
•Spontaneous dog cancers closely resemble human cancer.•Dogs with EGFR associated tumors were immunized with an EGFR/HER2 peptide vaccine.•EGFR peptide vaccinated dogs developed anti-EGFR/HER2 ...antibodies.•Vaccinated dogs have anti-EGFR antibody and T cells infiltrating tumors.•Vaccinated dogs with osteosarcoma had tumor regression and increased survival.
Epidermal Growth Factor Receptor (EGFR) is overexpressed on a number of human cancers, and often is indicative of a poor outcome. Treatment of EGFR/HER2 overexpressing cancers includes monoclonal antibody therapy (cetuximab/trastuzumab) either alone or in conjunction with other standard cancer therapies. While monoclonal antibody therapy has been proven to be efficacious in the treatment of EGFR/HER2 overexpressing tumors, drawbacks include the lack of long-lasting immunity and acquired resistance to monoclonal therapy. An alternative approach is to induce a polyclonal anti-EGFR/HER2 tumor antigen response by vaccine therapy. In this phase I/II open-label study, we examined anti-tumor immunity in companion dogs with spontaneous EGFR expressing tumors. Canine cancers represent an outbred population in which the initiation, progression of disease, mutations and growth factors closely resemble that of human cancers. Dogs with EGFR expressing tumors were immunized with a short peptide of the EGFR extracellular domain with sequence homology to HER2. Serial serum analyses demonstrated high titers of EGFR/HER2 binding antibodies with biological activity similar to that of cetuximab and trastuzumab. Canine antibodies bound both canine and human EGFR on tumor cell lines and tumor tissue. CD8 T cells and IgG deposition were evident in tumors from immunized dogs. The antibodies inhibited EGFR intracellular signaling and inhibited tumor growth in vitro. Additionally, we illustrate objective responses in reducing tumors at metastatic sites in host animals. The data support the approach of amplifying anti-tumor immunity that may be relevant in combination with other immune modifying therapies such as checkpoint inhibitors.
Spontaneous tumors in canines share significant genetic and histological similarities with human tumors, positioning them as valuable models to guide drug development. However, current translational ...studies have limited real world evidence as cancer outcomes are dispersed across veterinary clinics and genomic tests are rarely performed on dogs. In this study, we aim to expand the value of canine models by systematically characterizing genetic mutations in tumors and their response to targeted treatments. In total, we collect and analyze survival outcomes for 2119 tumor-bearing dogs and the prognostic effect of genomic alterations in a subset of 1108 dogs. Our analysis identifies prognostic concordance between canines and humans in several key oncogenes, including TP53 and PIK3CA. We also find that several targeted treatments designed for humans are associated with a positive prognosis when used to treat canine tumors with specific genomic alterations, underscoring the value of canine models in advancing drug discovery for personalized oncology.
Computer security is a balance between protecting information and enabling authorized access. Tightening security by making systems more inaccessible can hinder employees and make them less ...productive. It can also result in lower security as workers struggle to find ways around the security conditions to enable them to do their jobs. This study analyzes an information systems user survey to evaluate the tradeoffs between protection and accessibility. Over one-third of the respondents report problems with interference from security provisions. A structural equation model explores the impact of these effects on eventual security levels.
Purpose : 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.
Experimental Design : 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.
Results: 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).
Conclusions : 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.
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