Retrospective evaluation of the effect of acid suppressant drugs on leukocyte ratios in dogs with mast cell tumors.

BACKGROUND: Acid suppressant drugs (ASDs) are commonly used to decrease gastric acid production, but some evidence exists that ASDs exert immunomodulatory effects. Such an effect has not been investigated in dogs for which ASDs are routinely prescribed. HYPOTHESIS: Compared to naïve subjects, dogs treated with ASDs will exhibit differences in leukocyte ratios after treatment. ANIMALS: Fifty-one dogs with mast cell tumors (MCTs). MATERIALS AND METHODS: Dogs with MCT that were either AS naïve or treated with ASDs (i.e., histamine-2-receptor antagonists [H2RA] or proton pump inhibitors [PPI]) were included in this retrospective study. Subjects were categorized into 3 treatment groups (AS naïve, H2RA treated, and PPI treated), and leukocyte ratios (neutrophil:eosinophil, lymphocyte:monocyte, and neutrophil:lymphocyte [NLR]) were calculated before and after treatment. A mixed effects analysis of variance on ranks was used to assess differences in ratios between treatments, between pre- and post-treatment time points, and between pre- and post-time points for each treatment. Concurrent administration of antihistamines, corticosteroids, and chemotherapeutic drugs was assessed as a confounding factor. RESULTS: Famotidine (n = 14/14) and omeprazole (n = 12/12) were the only H2RA and PPI used, respectively. Dogs receiving famotidine had a significant increase in median NLR from pre- to post-treatment (3.429; range, 1.417-15 to 5.631; range, 2.654-92; P < 0.01) compared to PPI treated or AS naïve dogs. No differences existed in chemotherapeutic drug or corticosteroid use between groups. CONCLUSIONS: A significant difference in NLR was identified in famotidine treated dogs compared with omeprazole treated or AS naïve dogs.

Adjuvant Sirolimus Does Not Improve Outcome in Pet Dogs Receiving Standard-of-Care Therapy for Appendicular Osteosarcoma: A Prospective, Randomized Trial of 324 Dogs.

PURPOSE: The mTOR pathway has been identified as a key nutrient signaling hub that participates in metastatic progression of high-grade osteosarcoma. Inhibition of mTOR signaling is biologically achievable with sirolimus, and might slow the outgrowth of distant metastases. In this study, pet dogs with appendicular osteosarcoma were leveraged as high-value biologic models for pediatric osteosarcoma, to assess mTOR inhibition as a therapeutic strategy for attenuating metastatic disease progression. PATIENTS AND METHODS: A total of 324 pet dogs diagnosed with treatment-naïve appendicular osteosarcoma were randomized into a two-arm, multicenter, parallel superiority trial whereby dogs received amputation of the affected limb, followed by adjuvant carboplatin chemotherapy ± oral sirolimus therapy. The primary outcome measure was disease-free interval (DFI), as assessed by serial physical and radiologic detection of emergent macroscopic metastases; secondary outcomes included overall 1- and 2-year survival rates, and sirolimus pharmacokinetic variables and their correlative relationship to adverse events and clinical outcomes. RESULTS: There was no significant difference in the median DFI or overall survival between the two arms of this trial; the median DFI and survival for standard-of-care (SOC; defined as amputation and carboplatin therapy) dogs was 180 days [95% confidence interval (CI), 144-237] and 282 days (95% CI, 224-383) and for SOC + sirolimus dogs, it was 204 days (95% CI, 157-217) and 280 days (95% CI, 252-332), respectively. CONCLUSIONS: In a population of pet dogs nongenomically segmented for predicted mTOR inhibition response, sequentially administered adjuvant sirolimus, although well tolerated when added to a backbone of therapy, did not extend DFI or survival in dogs with appendicular osteosarcoma.

Evaluation of Zoledronate as Treatment for Hypercalcemia in Four Dogs.

Hypercalcemia is a biochemical abnormality that, when left untreated, can lead to life-threatening complications including renal failure. Bisphosphonates are routinely used to treat hypercalcemia, but most literature on veterinary patients describes the use of pamidronate. This retrospective case series describes the use of zoledronate for treatment of hypercalcemia in four dogs. Information including signalment, clinical signs, treatment, and outcome was collected. All dogs showed a decrease in total and ionized calcium concentrations after treatment with zoledronate. All treatments of zoledronate administered were well tolerated, but a previously unreported local hypersensitivity reaction was observed in one dog. This report is the first to document the efficacy of zoledronate for treatment of hypercalcemia in dogs.

Mechlorethamine, vincristine, melphalan and prednisolone rescue chemotherapy protocol for resistant feline lymphoma.

Objectives The goals of this retrospective study were to evaluate the use of mechlorethamine, vincristine, melphalan and prednisolone (MOMP) chemotherapy for rescue of feline lymphoma, to describe the protocol's toxicity and to determine prognostic indicators for progression-free survival. Methods The medical records of 12 cats treated with MOMP chemotherapy at the University of Tennessee Veterinary Medical Center between 2007 and 2017 were evaluated. Parameters assessed included lymphoma cell size, anatomical location, number of previous chemotherapy drugs and number of previous rescue protocols received. Chemotherapy-related toxicity was also described. Results Seven of 12 cats responded to this rescue protocol. Three cats experienced complete response and four cats achieved partial response for a median duration of 39 days (range 14-345 days). Cats that achieved complete response had a significantly longer median progression-free survival than cats that did not respond to treatment. Five of 12 cats developed hematologic toxicity (neutropenia) and one cat developed gastrointestinal toxicity. Toxicity was mild in most cases; no cats needed to be hospitalized. Neutropenia was associated with increased progression-free survival. Conclusions and relevance MOMP is a safe and effective rescue chemotherapy protocol for cats with relapsing and refractory lymphoma.