Effect of feeding a weight loss food beyond a caloric restriction period on body composition and resistance to weight gain in cats.

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.

Effect of feeding a weight loss food beyond a caloric restriction period on body composition and resistance to weight gain in dogs.

OBJECTIVE: To determine the effect of feeding a food with coconut oil and supplemental L-carnitine, lipoic acid, lysine, leucine, and fiber on weight loss and maintenance in dogs. DESIGN: Prospective clinical study. ANIMALS: 50 overweight dogs. PROCEDURES: The study consisted of 2 trials. During trial 1, 30 dogs were allocated to 3 groups (10 dogs/group) to be fed a dry maintenance dog 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 dogs was fed the test food and caloric intake was adjusted to maintain a weight loss rate of 1% to 2%/wk (weight loss phase). Next, each dog 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). Dogs were weighed and underwent dual-energy x-ray absorptiometry monthly. Metabolomic data were determined before (baseline) and after each phase. RESULTS: During trial 1, dogs in groups 2 and 3 lost significantly more weight than did those in group 1. During trial 2, dogs lost a significant amount of body weight and fat mass but retained lean body mass (LBM) during the weight loss phase and continued to lose body fat but gained LBM during the weight maintenance phase. Evaluation of metabolomic data suggested that fat metabolism and LBM retention were improved from baseline for dogs fed the test food. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that feeding overweight dogs the test food caused weight loss and improvements in body condition during the weight-maintenance phase, possibly because the food composition improved energy metabolism.

Evaluation of 12- and 24-month survival rates after treatment with masitinib in dogs with nonresectable mast cell tumors.

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.

A multicenter study of the effect of dietary supplementation with fish oil omega-3 fatty acids on carprofen dosage in dogs with osteoarthritis.

OBJECTIVE: To determine the effects of feeding a diet supplemented with fish oil omega-3 fatty acids on carprofen dosage in dogs with osteoarthritis. DESIGN: Randomized, controlled, multisite clinical trial. ANIMALS: 131 client-owned dogs with stable chronic osteoarthritis examined at 33 privately owned veterinary hospitals in the United States. PROCEDURES: In all dogs, the dosage of carprofen was standardized over a 3-week period to approximately 4.4 mg/kg/d (2 mg/lb/d), PO. Dogs were then randomly assigned to receive a food supplemented with fish oil omega-3 fatty acids or a control food with low omega-3 fatty acid content, and 3, 6, 9, and 12 weeks later, investigators made decisions regarding increasing or decreasing the carprofen dosage on the basis of investigator assessments of 5 clinical signs and owner assessments of 15 signs. RESULTS: Linear regression analysis indicated that over the 12-week study period, carprofen dosage decreased significantly faster among dogs fed the supplemented diet than among dogs fed the control diet. The distribution of changes in carprofen dosage for dogs in the control group was significantly different from the distribution of changes in carprofen dosage for dogs in the test group. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that in dogs with chronic osteoarthritis receiving carprofen because of signs of pain, feeding a diet supplemented with fish oil omega-3 fatty acids may allow for a reduction in carprofen dosage.

Multicenter veterinary practice assessment of the effects of omega-3 fatty acids on osteoarthritis in dogs.

OBJECTIVE: To assess the effect of food containing high concentrations of fish oil omega-3 fatty acids and a low omega-6-omega-3 fatty acid ratio on clinical signs of osteoarthritis in dogs. DESIGN: Randomized, double-blinded, controlled clinical trial. ANIMALS: 127 client-owned dogs with osteoarthritis in 1 or more joints from 18 privately owned veterinary clinics. PROCEDURES: Dogs were randomly assigned to be fed for 6 months with a typical commercial food or a test food containing a 31-fold increase in total omega-3 fatty acid content and a 34-fold decrease in omega-6-omega-3 ratio, compared with the control food. Dog owners completed a questionnaire about their dog's arthritic condition, and investigators performed a physical examination and collected samples for a CBC and serum biochemical analyses (including measurement of fatty acids concentration) at the onset of the study and at 6, 12, and 24 weeks afterward. RESULTS: Dogs fed the test food had a significantly higher serum concentration of total omega-3 fatty acids and a significantly lower serum concentration of arachidonic acid at 6, 12, and 24 weeks. According to owners, dogs fed the test food had a significantly improved ability to rise from a resting position and play at 6 weeks and improved ability to walk at 12 and 24 weeks, compared with control dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Ingestion of the test food raised blood concentrations of omega-3 fatty acids and appeared to improve the arthritic condition in pet dogs with osteoarthritis.

Evaluation of the effects of dietary supplementation with fish oil omega-3 fatty acids on weight bearing in dogs with osteoarthritis.

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.

Evaluation of radiotherapy alone or in combination with doxorubicin chemotherapy for the treatment of cats with incompletely excised soft tissue sarcomas: 71 cases (1989-1999).

OBJECTIVE: To determine whether the addition of doxorubicin chemotherapy affected the outcome of cats with incompletely excised, nonvisceral soft tissue sarcomas undergoing postoperative radiotherapy. DESIGN: Retrospective case series. ANIMALS: 71 cats. PROCEDURES: Medical records were reviewed for clinically relevant data on cats that underwent postoperative radiotherapy for treatment of incompletely excised soft tissue sarcomas with or without concurrent doxorubicin chemotherapy. Radiotherapy was performed on an alternate-day schedule, with a total dose of 58.8 to 63 Gy delivered in 21 fractions. Doxorubicin was administered every 21 days for 3 to 5 cycles. Follow-up information was obtained by means of physical examination or through telephone conversations with refer-ring veterinarians or owners. RESULTS: Median disease-free interval with concurrent radiotherapy and doxorubicin chemotherapy (15.4 months; range, 2.4 to 44.9 months) was significantly longer than median disease-free interval with radiotherapy alone (5.7 months; range, 1.0 to 50.8 months). However, survival time was not significantly different between groups. CONCLUSION AND CLINICAL RELEVANCE: Results suggested that doxorubicin chemotherapy may play a role in extending the disease-free interval in cats undergoing radiotherapy for treatment of incompletely excised soft tissue sarcomas.

Hematologic changes associated with half-body irradiation in dogs with lymphoma.

BACKGROUND: Reports describe the technique and efficacy of half-body irradiation (HBI) of dogs with lymphoma, but few describe the distinctive toxicoses associated with the combination of HBI and chemotherapy. HYPOTHESIS: HBI would transiently affect myelocytic and erythroid variables as assessed by serial analysis of complete blood counts. ANIMALS: Twenty-nine dogs with lymphoma treated with HBI during 2002 and 2003. METHODS: A retrospective study of medical records of 29 dogs was performed. Two HBI protocols were used, resulting in delivery of either 6 Gy or 8 Gy to each half of the body, 1 month apart. Dogs received chemotherapy before, during, or after irradiation, or at multiple times. Serial hematology was available for all dogs. Data were analyzed between collection periods by analysis of variance (ANOVA) RESULTS: The mean granulocyte count significantly (P < .01) decreased from 10,017 cells/microL (data range 3,001-20,170 cells/ microL) before the first radiation treatment to 3,250 cells/microL (820-4,400 cells/microL) at week 5 (P < .01). Three weeks after this nadir, the mean increased to 10,150 cells/microL (900-26,700 cells/microL). The hematocrit did not change (36-38%). Thrombocytopenia (<100,000/microL) occurred in 10 dogs. Two dogs died because of complications associated with thrombocytopenia. No significant difference in toxicity was found between the 6 Gy and 8 Gy group. CONCLUSIONS AND CLINICAL IMPORTANCE: HBI was myelosuppressive but effects were short term and resolved in 22 of 24 dogs. Further studies are needed to elucidate the safety and role of HBI in the treatment of dogs with lymphoma.

Single agent gemcitabine chemotherapy in dogs with spontaneously occurring lymphoma.

BACKGROUND: Gemcitabine has been shown to be effective as a single agent in a variety of tumors including nonHodgkin's lymphoma. Its use in veterinary medicine has been limited and to date this drug has not been used as a first-line therapy in dogs with lymphoma. HYPOTHESIS: Gemcitabine as a single agent may be efficacious in dogs presented for the first time with lymphoma. ANIMALS: Twenty-four dogs with spontaneously occurring lymphoma. METHODS: All dogs were clinically staged and given gemcitabine at 400 mg/m(2) over a 30-minute intravenous infusion weekly for 3 weeks and then given 1 week off treatment before starting a second cycle. RESULTS: A single dose of gemcitabine lowered both neutrophil count (decrease in mean neutrophil count from 10,640 cells/ microL to 3,140 cells/microL) and platelet count (decrease in mean platelet count from 201,290 cells/microL to 139,190 cells/microL) 7 days after administration. Consequently gemcitabine dosage was reduced at the second treatment in 8 of 21 dogs or a dose delay of 1-7 days and a reduction of dosage was used in 7 of 21 dogs. Seven dogs completed the assigned 4-week cycle. Two of these dogs had progressive disease and 5 had stable disease. No objective responses were seen in dogs treated with a second cycle of gemcitabine. CONCLUSIONS AND CLINICAL IMPORTANCE: Gemcitabine administration as a single agent resulted in hematologic toxicity and did not reduce lymphoma burden. If gemcitabine is to be used in veterinary medicine, additional prospective pharmacologic studies should be done to determine the appropriate dosage, regimen, and schedule of use before it can be recommended for use in the treatment of dogs with lymphoma as a single agent.

Efficacy of radiation therapy for incompletely resected grade-III mast cell tumors in dogs: 31 cases (1987-1998).

OBJECTIVE: To determine the efficacy (durations of remission and survival) of an alternating-day radiation protocol for incompletely excised histologic grade-III solitary mast cell tumors (MCTs) in dogs. DESIGN: Retrospective study. ANIMALS: 31 dogs. PROCEDURE: Radiation (52 Gy in an 18-fraction alternating-day protocol) was delivered to an area bordered by margins > or = 3 cm around the surgical scar and to the associated local-regional lymph nodes. Dogs were not given chemotherapeutic agents concurrently or after radiation. Information on signalment, duration of remission, and survival time was obtained from medical records. RESULTS: Median and mean durations of remission were 27.7 and 17.0 months, respectively (range, 1 to 47 months). Median and mean durations of survival were 28 and 20 months, respectively (range, 3 to 52 months). Dogs with tumors located on the skin of the pinna, perineum, and prepuce had a median duration of remission greater than dogs with tumors located at other sites (27.7 and 14.4 months, respectively). Dogs with tumors < or = 3 cm in maximum diameter before surgery survived longer than dogs with tumors > 3 cm (31 and 24 months, respectively). The remission rate was 65% and survival rate was 71% at 1 year after treatment. Sixteen dogs that were euthanatized had complications associated with local-regional tumor progression. Systemic metastases to liver, spleen, intestine, and bone marrow were detected in 1 dog. CONCLUSIONS AND CLINICAL RELEVANCE: Without further treatment, incompletely excised grade-III mast cell tumors have high local-regional recurrence; local-regional treatment with radiation may effectively be used to manage many such tumors.

Treatment of dogs with oral melanoma by hypofractionated radiation therapy and platinum-based chemotherapy (1987-1997).

This retrospective study in 39 dogs with incompletely resected oral melanoma examined the efficacy of hypofractionated radiation therapy and platinum-containing chemotherapy. All dogs were completely staged, with the majority of dogs classified as stage 1. Dogs received 6 weekly fractions of 6-gray (Gy) megavoltage irradiation with a cobalt-60 unit or a 4-MeV (megaelectron volts) linear accelerator. Dogs received cisplatin (10-30 mg/m2 IV) or carboplatin (90 mg/m2 IV) chemotherapy 60 minutes before radiation delivery. Durations of local control, metastasis-free survival time, and overall survival time were recorded. By the Kaplan-Meier method, 15% of the dogs had local recurrence within a median time of 139 days. Fifty-one percent of the dogs developed metastatic disease within a median time of 311 days (range, 24-2, 163 days). Median survival time for all 39 dogs was 363 days. The combined use of chemotherapy and radiation therapy in this protocol provided local control consistent with previous studies. Low-dose chemotherapy was used with the intent of enhancing radiation therapy for the local control of an incompletely excised tumor. Survival times were longer than previously reported for dogs with oral malignant melanoma. Additional studies are required to determine whether these results were due to the effects of chemotherapy on microscopic disease or the enhanced local control provided by chemoradiation therapy.

Effects of plasmid-mediated growth hormone-releasing hormone in severely debilitated dogs with cancer.

Cachexia is a common manifestation of late stage malignancy and is characterized by anemia, anorexia, muscle wasting, loss of adipose tissue, and fatigue. Although cachexia is disabling and can diminish the life expectancy of cancer patients, there are still no effective therapies for this condition. We have examined the feasibility of using a myogenic plasmid to express growth hormone-releasing hormone (GHRH) in severely debilitated companion dogs with naturally occurring tumors. At a median of 16 days after intramuscular delivery of the plasmid, serum concentrations of insulin-like growth factor I (IGF-I), a measure of GHRH activity, were increased in 12 of 16 dogs (P < 0.01). These increases ranged from 21 to 120% (median, 49%) of the pretreatment values and were generally sustained or higher on the final evaluation. Anemia resolved posttreatment, as indicated by significant increases in mean red blood cell count, hematocrit, and hemoglobin concentrations, and there was also a significant rise in the percentage of circulating lymphocytes. Treated dogs maintained their weights over the 56-day study and did not show any adverse effects from the GHRH gene transfer. We conclude that intramuscular injection of a GHRH-expressing plasmid is both safe and capable of stimulating the release of growth hormone and IGF-I in large animals. The observed anabolic responses to a single dose of this therapy might be beneficial in patients with cancer-associated anemia and cachexia.

Evaluation of treatment with doxorubicin and piroxicam or doxorubicin alone for multicentric lymphoma in dogs.

OBJECTIVE: To evaluate the antitumor and toxic effects of treatment with doxorubicin combined with piroxicam or doxorubicin alone for multicentric lymphoma in dogs. DESIGN: Nonrandomized clinical trial. ANIMALS: 75 dogs with multicentric lymphoma. PROCEDURE: 33 dogs were treated with doxorubicin (30 mg/m2, IV, q 21 d, for 3 doses) and piroxicam (0.3 mg/kg [0.14 mg/lb], PO, q 24 h); results were compared with a historical control group of 42 dogs treated with doxorubicin (30 mg/M2, IV, q 21 d, for 3 doses) alone. Results-The percentages of dogs that had remission with doxorubicin-piroxicam treatment (79%) or doxorubicin treatment alone (74%) were not significantly different. Median duration of first remission was 130 days with doxorubicin-piroxicam and 147 days with doxorubicin alone; these values were not significantly different. Severe toxicosis was observed in 22% of dogs treated with doxorubicin-piroxicam and 17% of dogs treated with doxorubicin alone. CONCLUSIONS AND CLINICAL RELEVANCE: Both treatment protocols were efficacious and well tolerated. The doxorubicin-piroxicam treatment was no more effective regarding response rate, remission duration, or survival duration, compared with the control group treated with doxorubicin alone.

Photodynamic therapy response in cats with cutaneous squamous cell carcinoma as a function of fluence.

The response of advanced stage cutaneous squamous cell carcinomas (SCC) following treatment with photodynamic therapy (PDT) has been poor. It was the aim of this pilot study to determine whether an increase in the delivered fluence (i.e. energy density) would improve the duration of tumour remission in cats with advanced-stage SCC. Tumours were treated with aluminium phthalocyanine tetrasulphonate (AlPcS4 ) PDT at a fluence of either 100 J cm-2 or 200 J cm-2 and tumour response was evaluated at regular intervals. Those feline tumours treated with a fluence of 100 J cm-2 (n= 8) had a significantly shorter median remission duration (69 days; range 0-619 days) than those feline tumours treated with 200 J cm-2 (n= 6; 522 days; range 151-1057 days). It is our conclusion that a fluence of 200 J cm-2 is well tolerated and more effective when treating cats with advanced stage cutaneous SCC.

Hematologic changes associated with weekly low-dose cisplatin administration in dogs.

This study prospectively describes the systemic toxicity of cisplatin (20 mg/m(2),IV) when given in weekly doses prior to localized irradiation in dogs with solid malignancies. Eleven dogs received a total of 54 weekly doses of cisplatin. Two dogs did not complete the 5-week protocol due to progressive disease and two dogs received 6 weekly doses of cisplatin. Repeated administration of cisplatin caused a significant decline in the leukocyte count, segmented neutrophil count, and platelet count. These changes were related to the number of cisplatin doses. The dogs did not have any significant alteration of blood urea nitrogen, serum creatinine, or urine specific gravity during the treatment period. Weekly low-dose cisplatin, as used in this study, is safe for use in tumor-bearing dogs. However, the significant decline in the leukocyte, segmented neutrophil, and platelet counts in these 11 dogs suggest that cisplatin prescribed at 20 mg/m(2) IV once per week should not exceed five consecutive treatments.

Detection of serum alpha-fetoprotein in dogs with naturally occurring malignant neoplasia.

Serum alpha-fetoprotein (AFP) concentrations were determined, by use of an automated microparticle enzyme-linked immunoassay (MEIA), in 16 control dogs and 48 dogs with previously untreated, histologically confirmed, naturally occurring neoplasia (17 dogs with lymphoma and 31 dogs with nonhematopoietic malignancies, 13 dogs with carcinomas, 18 dogs with sarcomas). Mean serum AFP concentrations for untreated dogs with lymphoma, for dogs with sarcomas, and for dogs with carcinomas were not significantly different from the mean serum AFP concentration for the 16 untreated control dogs. Mean serum AFP concentration for dogs with transitional cell carcinoma (n=7) was not significantly different from the mean serum AFP concentration for the control dogs. It has been shown previously by others that a mean serum AFP concentration > 225 ng/mL is suggestive of a hepatic malignancy (e.g., hepatocellular carcinoma, lymphoma). In our study, all 48 dogs had a normal complete blood count, serum biochemical analysis, and urinalysis. Only one of the 48 dogs was found to have a serum AFP concentration > 225 ng/mL. Later evaluation of this dog confirmed hepatic involvement with lymphoma. AFP can be detected in the serum of dogs with naturally occurring tumors using the MEIA technique. A serum AFP concentration above that observed in normal dogs is not a common finding in dogs with naturally occurring neoplasia; however, we confirmed that a serum AFP concentration > 225 ng/mL, with or without evidence of a serum biochemical abnormality, may suggest primary and/or secondary hepatic involvement with a neoplastic disease and may warrant an adjustment in clinical stage and prognosis. A prospective diagnostic and therapeutic evaluation of dogs, with naturally occurring tumors having an elevated serum AFP concentration would determine the validity of this conclusion.