Impact of Toceranib/Piroxicam/Cyclophosphamide Maintenance Therapy on Outcome of Dogs with Appendicular Osteosarcoma following Amputation and Carboplatin Chemotherapy: A Multi-Institutional Study.

BACKGROUND: We 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 FINDINGS: This 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. CONCLUSIONS: The 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.

Retrospective evaluation of the effectiveness of epsilon aminocaproic acid for the prevention of postamputation bleeding in retired racing Greyhounds with appendicular bone tumors: 46 cases (2003-2008).

OBJECTIVES: To determine the frequency of delayed postoperative bleeding in retired racing Greyhounds with appendicular bone tumors undergoing limb amputations. To identify if administration of epsilon-aminocaproic acid (EACA) was effective on the prevention of postoperative bleeding. DESIGN: Retrospective study from December 2003 to December 2008. SETTING: Veterinary university teaching hospital. ANIMALS: Forty-six retired racing Greyhounds (RRGs) diagnosed with primary appendicular bone tumors that underwent limb amputation were included in the study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Thirteen of 46 RRGs (28%) included in the study had delayed postoperative bleeding starting 48-72 h after surgery. Bleeding episodes included cutaneous, subcutaneous, and external bleeding that extended from the area of the surgical site that became widespread within hours, and that required administration of blood components. A paired t-test suggests that there was a significant decrease in PCV postoperatively for both dogs that bled and dogs that did not bleed (P < 0.0001). Forty of 46 RRGs (86%) received either fresh frozen plasma (FFP) or EACA or both, for the prevention of postoperative bleeding. A logistic regression model determined that dogs that did not receive EACA were 5.7 times more likely to bleed than dogs that did receive EACA, when controlling for whether or not they received FFP (95% CI: 1.02-32.15, P = 0.047). CONCLUSION: This retrospective study suggests that preemptive postoperative administration of EACA appears to be efficacious in decreasing the frequency of bleeding in RRGs undergoing limb amputation; however, a prospective study is warranted to corroborate its effectiveness.

Blood gas analysis and cooximetry in retired racing Greyhounds.

OBJECTIVE: The purposes of this study were to evaluate the oxygen affinity of hemoglobin (Hb) in healthy retired racing Greyhounds via cooximetry, and to establish reference intervals for blood gases and cooximetry in this breed. DESIGN: Prospective clinical study. SETTING: University Teaching Hospital. ANIMALS: Fifty-seven Greyhounds and 30 non-Greyhound dogs. INTERVENTIONS: Venous blood samples were collected from the jugular vein and placed into heparinized tubes. The samples were analyzed within 30 minutes of collection using a blood gas analyzer equipped with a cooximeter. MEASUREMENTS AND MAIN RESULTS: Greyhounds had significantly higher pH, PO(2) , oxygen saturation, oxyhemoglobin, total Hb, oxygen content, and oxygen capacity and significantly lower deoxyhemoglobin and P(50) when compared with non-Greyhound dogs. CONCLUSION: These findings support the fact that this breed is able to carry a higher concentration of total oxygen in the blood. As reported previously, this breed also has lower P(50) and, therefore, high oxygen affinity. In light of recent findings suggesting that in certain tissues a high affinity for oxygen is beneficial, this adaptation may be of benefit during strenuous exercise.

Thromboelastography in healthy horses and horses with inflammatory gastrointestinal disorders and suspected coagulopathies.

OBJECTIVES: To evaluate the use of citrated recalcified (nonactivated) thromboelastography (TEG) in healthy horses and horses with colitis and suspected coagulopathies. DESIGN: Prospective, observational study conducted between October 2007 and June 2009. SETTING: Veterinary Teaching Hospital. ANIMALS: Forty-five healthy adult horses and 12 sick adult horses with colitis and prolonged prothrombin time (PT) or activated partial thromboplastin time (aPTT). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Whole blood was collected on admission. Coagulation profile (PT, aPTT, platelet count, and fibrinogen concentration) and citrated recalcified whole blood TEG analysis (R-time [R], K-time [K], angle [α], maximum amplitude [MA], G value [G], lysis at 60 min [LY60]) were evaluated. Mean values (SD) for TEG parameters in healthy horses were: R=10.4 (3.1) minutes; K=3.5 (1.2) minutes; α=46.3 (11.0)°; MA=55.6 (5.1) mm; G=6,429 (1,341) dyn/cm², and LY60=5.1 (2.4)%. Mean coefficients of variation for intra-assay/interindividual variability in healthy horses were: R=4.7%/30.7%, K=4.8%/35.3%, α=4.4%/23.8%, MA=1.4%/9.3%, G=3.4%/20.8%, and LY60=13.1%/47.7%, respectively. Horses with colitis and prolonged PT and/or aPTT had longer mean values for R (P<0.001) and K (P<0.001), narrower mean α (P<0.001), decreased mean MA (P=0.001), and smaller mean G (P=0.02); changes consistent with hypocoagulability. CONCLUSIONS: Citrated recalcified (nonactivated) TEG demonstrated changes consistent with hypocoagulability in horses with colitis that had preidentified coagulation abnormalities. This technique has high interindividual variability and low intra-assay variability. TEG may be useful for detecting hypocoagulable states in horses with colitis and suspected coagulopathies.