The purpose of this study was to provide an initial assessment of the potential biologic activity of toceranib phosphate (Palladia®) in select solid tumors in dogs. Cases in which toceranib was used to treat dogs with anal sac anal gland adenocarcinoma, metastatic osteosarcoma, thyroid carcinoma, head and neck carcinoma, and nasal carcinoma were included. Clinical benefit (CB) was observed in 63/85 (74%) dogs including 28/32 anal sac tumors (8PR, 20SD), 11/23 osteosarcomas (1PR, 10SD), 12/15 thyroid carcinomas (4PR, 8SD), 7/8 head and neck carcinomas (1CR, 5PR, 1SD) and 5/7 (1CR, 4SD) nasal carcinomas. For dogs experiencing CB, the median dose of toceranib was 2.8 mg/kg, 36/63 (58.7%) were dosed on a Monday/Wednesday/Friday basis, and 47/63 (74.6%) were treated 4 months or longer. While these data povide preliminary evidence that toceranib exhibits CB in dogs with certain solid tumors, future prospective studies are necessary to define its true activity.

BackgroundWe hypothesized that the addition of toceranib to metronomic cyclophosphamide/piroxicam therapy would significantly improve disease-free interval (DFI) and overall survival (OS) in dogs with appendicular osteosarcoma (OSA) following amputation and carboplatin chemotherapy.Methods and FindingsThis was a randomized, prospective clinical trial in which dogs with OSA free of gross metastatic disease (n = 126) received carboplatin chemotherapy (4 doses) following amputation. On study entry, dogs were randomized to receive piroxicam/cyclophosphamide with or without toceranib (n = 63 each) after completing chemotherapy. Patient demographics were not significantly different between both groups. During or immediately following carboplatin chemotherapy, 32 dogs (n = 13 toceranib; n = 19 control) developed metastatic disease, and 13 dogs left the study due to other medical conditions or owner preference. Following carboplatin chemotherapy, 81 dogs (n = 46 toceranib; n = 35 control) received the metronomic treatment; 35 dogs (n = 20 toceranib; n = 15 control) developed metastatic disease during the maintenance therapy, and 26 dogs left the study due to other medical conditions or owner preference. Nine toceranib-treated and 11 control dogs completed the study without evidence of metastatic disease 1-year following amputation. Toceranib-treated dogs experienced more episodes of diarrhea, neutropenia and weight loss than control dogs, although these toxicities were low-grade and typically resolved with supportive care. More toceranib-treated dogs (n = 8) were removed from the study for therapy-associated adverse events compared to control dogs (n = 1). The median DFI for control and toceranib treated dogs was 215 and 233 days, respectively (p = 0.274); the median OS for control and toceranib treated dogs was 242 and 318 days, respectively (p = 0.08). The one year survival rate for control dogs was 35% compared to 38% for dogs receiving toceranib.ConclusionsThe addition of toceranib to metronomic piroxicam/cyclophosphamide therapy following amputation and carboplatin chemotherapy did not improve median DFI, OS or the 1-year survival rate in dogs with OSA.

Background Appendicular osteosarcoma (OSA), the most common bone tumor in dogs, is typically treated by amputation and adjuvant chemotherapy. Despite numerous efforts, the median survival time (MST) for dogs receiving a platinum compound, doxorubicin, or a combination of these remains at 8–12 months. Evidence from studies in mice suggests that gemcitabine has activity against OSA in vivo. Our preliminary work demonstrated that the addition of low-dosage (10mM) gemcitabine to carboplatin resulted in synergistic inhibition of OSA cell viability in vitro. Objective The purpose of the following study was to determine whether the addition of low-dosage (2 mg/kg) gemcitabine to carboplatin chemotherapy in dogs with OSA after amputation would improve MST over carboplatin monotherapy. Animals Fifty dogs with histologically confirmed appendicular OSA. Methods Dogs were treated prospectively with amputation and up to 4 dosages of carboplatin and gemcitabine in combination every 3 weeks. Results The chemotherapeutic regimen was well tolerated with only 5 episodes of grade 3 or 4 hematologic toxicity. The median disease-free interval (DFI) was 203 days and the MST was 279 for all dogs in this study. The 1- and 2-year survival rates were 29.5 and 11.3%, respectively. Dogs with proximal humeral OSA had a shorter median DFI (P = .04) compared with dogs with OSA in other locations. Conclusions and Clinical Importance These results are comparable to those reported for carboplatin monotherapy indicating that the addition of gemcitabine to carboplatin in dogs with appendicular OSA does not appear to improve outcome.

OBJECTIVE To describe the outcome of dietary management of canine noninfectious acute colitis with or without concurrent oral administration of metronidazole using a randomized controlled clinical trial. ANIMALS 59 client-owned dogs with noninfectious acute colitis. PROCEDURES Dogs with acute noninfectious colitis were enrolled in a 30-day diet trial after exclusion of parasitic infectious etiologies (fecal centrifugation floatation, Giardia/Cryptosporidium antigen testing) and systemic disease (CBC, biochemistry, urinalysis). Dogs were randomized into 3 placebo-controlled groups: group 1, easily digestible diet + placebo tablet; group 2, easily digestible diet + metronidazole tablet; and group 3, psyllium-enhanced easily digestible diet + placebo tablet. Dogs were evaluated serially using fecal scoring for time to remission, average fecal score, relapse after remission, and dysbiosis index. RESULTS Median remission time was significantly different among the 3 groups (P < .01) with median times of 5 days (range, 4 to 10) for group 1, 8.5 days (range, 7 to 12) for group 2, and 5 days (range, 3 to 6) for group 3. Metronidazole addition affected the fecal dysbiosis index negatively at days 7 to 10. No adverse effects or complications were noted throughout the study. CLINICAL RELEVANCE For canine noninfectious acute colitis, dietary management with an easily digestible diet with or without psyllium enhancement proved a superior management strategy compared to metronidazole. The omission of metronidazole reduced the adverse impact significantly on intestinal microbiota. Longitudinal clinical trials are necessary to compare the long-term response, stability, and complications associated with dietary management alone versus combined dietary and antimicrobial therapy for canine acute colitis.