Plasma ammonia concentration after L-asparaginase therapy in 27 dogs with high-grade lymphoma or leukemia.

OBJECTIVES: To establish the occurrence of increased plasma ammonia concentration after L-asparaginase (L-asp) administration in dogs with high-grade lymphoma or leukemia; to identify risk factors for the development of hyperammonemia after L-asp administration; and to determine occurrence of adverse events related to hyperammonemia. DESIGN: Prospective case controlled study of sequentially enrolled dogs between May 2011 and March 2012. SETTING: A university veterinary teaching hospital. ANIMALS: Twenty-seven dogs with high-grade lymphoma or leukemia. INTERVENTIONS: All dogs received L-asp intramuscularly at a median dose of 400 IU/kg. MEASUREMENTS AND MAIN RESULTS: Plasma ammonia concentrations were measured at baseline, 16 hours, and 48 hours after L-asp therapy. Clinicopathological abnormalities were assessed to determine risk factors for the development of hyperammonemia. Adverse events following L-asp were recorded. Median plasma ammonia concentrations at baseline, 16 hours, and 48 hours were 26 µmol/L (44 µg/dL), 98 µmol/L (166.9 µg/dL), and 67 µmol/L (114 µg/dL), respectively. Median plasma ammonia concentrations at 16 and 48 hours after administration were significantly increased compared to baseline. Six dogs had adverse events following L-asp administration. No significant clinical signs were noted that could clearly be attributed to hyperammonemia. No risk factors for developing hyperammonemia were identified; however, there was a positive correlation between the development of hyperammonemia at 16- and 48-hour time points. CONCLUSIONS: Subclinical hyperammonemia in dogs with lymphoma or leukemia after L-asp administration appears to be common. No risk factors were identified for the development of hyperammonemia after L-asp treatment, and severe adverse events were rare.

Apoptotic effects of the tyrosine kinase inhibitor, masitinib mesylate, on canine osteosarcoma cells.

Osteosarcoma (OSA) is the most common primary bone tumor in dogs and the guarded prognosis highlights the necessity to find new treatments. Masitinib mesylate is a highly selective tyrosine kinase inhibitor that predominantly targets c-Kit and PDGFR-α/ß. This study evaluated the in-vitro activity of masitinib against three canine OSA cell lines after treatment with increasing concentrations of masitinib (0.1-50 µmol/l) at 24, 48, and 72 h. The IC50 values at 72 h for the three OSA cell lines (POS, HMPOS, and COS31) were determined to be 11.04, 7.09, and 9.74 µmol/l, respectively. In addition, increases in caspase-3/7 activity and transferase dUTP nick end labeling-positive cells indicated apoptotic cell death. Because increased levels of vascular endothelial growth factor are found in dogs with OSA, vascular endothelial growth factor in the supernatant was quantified. Overall, the study found that masitinib causes dose-time dependent OSA cell death in vitro through initiation of caspase-mediated apoptosis, which supports future OSA clinical trials.

Evaluation of the University of Florida lomustine, vincristine, procarbazine, and prednisone chemotherapy protocol for the treatment of relapsed lymphoma in dogs: 33 cases (2003-2009).

OBJECTIVE: To evaluate the toxicity and efficacy of a modification of a previously evaluated combination of lomustine, vincristine, procarbazine, and prednisone (LOPP) as a rescue protocol for refractory lymphoma in dogs. DESIGN: Retrospective case series. Animals-33 dogs with a cytologic or histologic diagnosis of lymphoma that developed resistance to their induction chemotherapy protocol. PROCEDURES: Lomustine was administered on day 0 of the protocol. Vincristine was administered on day 0 and again 1 time on day 14. Procarbazine and prednisone were administered on days 0 through 13 of the protocol. This cycle was repeated every 28 days. RESULTS: Median time from initiation to discontinuation of the University of Florida LOPP protocol was 84 days (range, 10 to 308 days). Overall median survival time was 290 days (range, 51 to 762 days). Overall response rate with this protocol was 61% (20/33), with 36% (12) having a complete response and 24% (8) having a partial response. Toxicosis rates were lower than for the previously published LOPP protocol. CONCLUSIONS AND CLINICAL RELEVANCE: The University of Florida LOPP protocol may be an acceptable alternative to the mechlorethamine, vincristine, procarbazine, and prednisone protocol as a rescue protocol for dogs with lymphoma.