OBJECTIVE To determine the lomustine content (potency) in compounded and FDA-approved lomustine capsules. DESIGN Evaluation study. SAMPLE 2 formulations of lomustine capsules (low dose [7 to 11 mg] and high dose [40 to 48 mg]; 5 capsules/dose/source) from 3 compounders and from 1 manufacturer of FDA-approved capsules. PROCEDURES Lomustine content was measured by use of a validated high-pressure liquid chromatography method. An a priori acceptable range of 90% to 110% of the stated lomustine content was selected on the basis of US Pharmacopeia guidelines. RESULTS The measured amount of lomustine in all compounded capsules was less than the stated content (range, 59% to 95%) and was frequently outside the acceptable range (failure rate, 2/5 to 5/5). Coefficients of variation for lomustine content ranged from 4.1% to 16.7% for compounded low-dose capsules and from 1.1% to 10.8% for compounded high-dose capsules. The measured amount of lomustine in all FDA-approved capsules was slightly above the stated content (range, 104% to 110%) and consistently within the acceptable range. Coefficients of variation for lomustine content were 0.5% for low-dose and 2.3% for high-dose FDA-approved capsules. CONCLUSIONS AND CLINICAL RELEVANCE Compounded lomustine frequently did not contain the stated content of active drug and had a wider range of lomustine content variability than did the FDA-approved product. The sample size was small, and larger studies are needed to confirm these findings; however, we recommend that compounded veterinary formulations of lomustine not be used when appropriate doses can be achieved with FDA-approved capsules or combinations of FDA-approved capsules.

Objective-To determine the effect of feeding a food with coconut oil and supplemental L-carnitine, lysine, leucine, and fiber on weight loss and maintenance in cats.Design-Prospective clinical study.Animals-50 overweight cats.Procedures-The study consisted of 2 trials. During trial 1, 30 cats were allocated to 3 groups (10 cats/group) to be fed a dry maintenance cat food to maintain body weight (group 1) or a dry test food at the same amount on a mass (group 2) or energy (group 3) basis as group 1. During trial 2, each of 20 cats was fed the test food and caloric intake was adjusted to maintain a weight loss rate of 1%/wk (weight loss phase). Next, each cat was fed the test food in an amount calculated to maintain the body weight achieved at the end of the weight loss phase (weight maintenance phase). Cats were weighed and underwent dual-energy x-ray absorptiometry monthly. Metabolomic data were determined before (baseline) and after each phase.Results-During trial 1, cats in groups 2 and 3 lost significantly more weight than did those in group 1. During trial 2, cats lost a significant amount of body weight and fat mass but retained lean body mass during the weight loss phase and continued to lose body weight and fat mass but gained lean body mass during the weight maintenance phase. Evaluation of metabolomic data suggested that fat metabolism was improved from baseline for cats fed the test food.Conclusions and Clinical Relevance-Results suggested that feeding overweight cats the test food caused weight loss and improvements in body condition during the weight maintenance phase, possibly because the food composition improved energy metabolism.

BACKGROUND ABT-751 is a novel orally available antimitotic agent that targets microtubule polymerization. This mechanism may suggest potential activity in canine lymphoma. OBJECTIVE Determine a maximum tolerated dose for ABT-751, and assess long-term tolerability and activity in canine lymphoma. ANIMALS Thirty dogs with newly diagnosed (n = 19) or relapsed (n = 11) non-Hodgkin's lymphoma. METHODS Dogs (n = 11) were enrolled in a rapid dose escalation study to define the maximum tolerated dose. Upon definition of a maximally tolerated dose, a cohort expansion of 19 dogs allowed verification of long-term tolerability and assessment of activity. Study endpoints in the cohort expansion included chronic tolerability, response rate, response duration, and time to progression. Additional endpoints included serum pharmacokinetics, lymph node drug concentrations, and changes in circulating endothelial cells. RESULTS The maximum tolerated dose of ABT-751 was 350 mg/m(2) PO q24h. Dose-limiting toxicities included vomiting and diarrhea, which resolved with a schedule adjustment to 350 mg/m(2) PO q48h. ABT-751 was consistently detected in lymphoma tissue samples from dogs treated at or above the maximum tolerated dose. In the cohort expansion, objective responses were seen in 3/15 (20%) dogs with a response duration ranging from 21 to 111 days. Decreases in circulating endothelial cells were seen in 10 dogs at day 7 (2 responding dogs and 8 nonresponding dogs). CONCLUSION ABT-751 was well tolerated at 350 mg/m(2) PO q24h for 7 days and then q48h thereafter. Activity of ABT-751 suggested a rationale for additional studies of ABT-751 as part of a combination chemotherapy protocol for lymphoma or other canine cancers.

Background: Tumors have heterogeneous properties, which could be explained by the existence of hierarchically and biologically distinct tumor cells such as tumor‐initiating cells (TICs). This model is clinically important, as TICs are promising targets for cancer therapies. However, TICs in spontaneous B‐cell lymphoma have not been conclusively identified.Hypothesis/Objectives: Tumor cells with a progenitor phenotype exist in B‐cell lymphoma, reflecting a hierarchical organization.Animals: Twenty‐eight client‐owned dogs with previously untreated B‐cell lymphoma and 6 healthy dogs.Methods: This was a prospective study. Flow cytometry was used to identify lymphoid progenitor cells (LPCs) that coexpressed hematopoietic progenitor antigens CD34, CD117, and CD133, with lymphoid differentiation markers CD21 and/or CD22 in B‐cell lymphoma. The polymerase chain reaction for antigen receptor rearrangements was used to analyze clonality and relatedness of tumor populations. A xenograft model with NOD/SCID/IL‐2Rγ−/− mice was adapted to expand and serially transplant primary canine B‐cell lymphoma.Results: LPCs were expanded in lymph nodes from 28 dogs with B‐cell lymphoma compared with 6 healthy dogs (P= .0022). LPCs contained a clonal antigen receptor gene rearrangement identical to that of the bulk of tumor cells. Canine B‐cell lymphoma xenografts in recipient mice that maintained LPCs in the tumors were recurrently observed.Conclusions and Clinical Importance: These results suggest the presence of a hierarchy of tumor cells in B‐cell lymphoma as has been demonstrated in other cancers. These findings have the potential to impact not only the understanding of lymphoma pathogenesis but also the development of lymphoma therapies by providing novel targets for therapy.

The purpose of this study was to describe cartilage and bone biochemical markers and body composition in growing large breed dogs and to determine if these masurements are affected by diets of similar caloric density but differing composition.

OBJECTIVE To evaluate the effectiveness of masitinib for the treatment of nonresectable mast cell tumors (MCTs) in dogs at 12 and 24 months after onset of treatment. ANIMALS 132 dogs with nonresectable grade 2 or 3 MCTs. PROCEDURES Dogs received masitinib (12.5 mg/kg/d, PO; n = 106) or a placebo (26). After 6 months, treatment was extended with tumor assessments at 3-month intervals until detection of disease progression. Endpoints were tumor response and overall survival rate and time. RESULTS In dogs with nonresectable MCTs, masitinib significantly improved survival rate, compared with results for the placebo, with 59 of 95 (62.1%) and 9 of 25 (36.0%) dogs alive at 12 months and 33 of 83 (39.8%) and 3 of 20 (15.0%) dogs alive at 24 months, respectively. Median overall survival time was 617 and 322 days, respectively. Tumor control at 6 months had a high predictive value for 24-month survival, with high specificity (88%) and sensitivity (76%), whereas short-term tumor response (within 6 weeks) had a poor predictive value. Complete responses at 24 months were observed in 6 of 67 (9.0%) dogs with nonresectable MCTs treated with masitinib. CONCLUSIONS AND CLINICAL RELEVANCE Masitinib significantly increased survival rates at 12 and 24 months in dogs with nonresectable MCTs. Control of disease at 6 months, but not best response at 6 weeks, was predictive of long-term survival in dogs treated with masitinib, which suggested that short-term response may be irrelevant for assessing clinical efficacy of tyrosine kinase inhibitors for treatment of MCTs.

OBJECTIVE To evaluate the effects of a food supplemented with fish oil omega-3 fatty acids on weight bearing in dogs with osteoarthritis. DESIGN Randomized, double-blinded, controlled clinical trial. ANIMALS 38 client-owned dogs with osteoarthritis examined at 2 university veterinary clinics. PROCEDURES Dogs were randomly assigned to receive a typical commercial food (n = 16) or a test food (22) containing 3.5% fish oil omega-3 fatty acids. On day 0 (before the trial began) and days 45 and 90 after the trial began, investigators conducted orthopedic evaluations and force-plate analyses of the most severely affected limb of each dog, and owners completed questionnaires to characterize their dogs' arthritis signs. RESULTS The change in mean peak vertical force between days 90 and 0 was significant for the test-food group (5.6%) but not for the control-food group (0.4%). Improvement in peak vertical force values was evident in 82% of the dogs in the test-food group, compared with 38% of the dogs in the control-food group. In addition, according to investigators' subjective evaluations, dogs fed the test food had significant improvements in lameness and weight bearing on day 90, compared with measurements obtained on day 0. CONCLUSIONS AND CLINICAL RELEVANCE At least in the short term, dietary supplementation with fish oil omega-3 fatty acids resulted in an improvement in weight bearing in dogs with osteoarthritis.

A study was conducted to determine differences in 29 healthy geriatric dogs (initially 13.51 ± 1.66 kg, 10.7 ± 2.33 years) with no radiographic evidence of arthritis or lameness history compared with 31 arthritic dogs (initially 13.5 ± 1.27 kg, 11.0 ± 2.23 years) with varying degrees of radiographic evidence of osteoarthritis and a history of lameness. All dogs were fed a maintenance control food for 28 days prior to sample collection. Blood samples were drawn into PAXgene blood RNA tubes at day 28 and RNA was extracted according to the procedures provided in the PAXgene RNA Kit Handbook (Qiagen, Valencia, CA). Probes were generated based on the canine genome sequencing for 89 arthritis related genes for RT‐PCR analysis based on previous literature. Transcripts having a P < 0.05 (following a false discovery rate adjustment) and a fold change range of at least 1.25 were considered different among the two groups. Analysis of the RNA found differences in 23 genes between the blood of osteoarthritic and healthy geriatric dogs. Of the genes identified, 22 were down‐regulated and 1 up‐regulated. Several of these genes have also been analyzed for in canine articular cartilage, however, the majority of them are elevated in OA vs healthy cartilage. Similar to human data, an inverse relationship of genes associated with osteoarthritis between blood and articular cartilage may exist in the dog.