Retrospective analysis of factors affecting clinical outcome following CHOP-based chemotherapy in dogs with primary nodal diffuse large B-cell lymphoma.

Numerous factors are known to affect the prognosis of dogs with chemotherapy-treated lymphomas. However, prognostic factors for dogs with specific subtypes of lymphoma are less clearly defined. The objective of this study was to identify prognostic factors for dogs receiving CHOP-based chemotherapy for primary nodal diffuse large B-cell lymphoma (DLBCL). Medical records of dogs treated for DLBCL at the Purdue Veterinary Teaching Hospital (PUVTH) from 2006 to 2016 were reviewed. Factors potentially related to prognosis were analysed using multivariable statistical methods. Ninety-eight dogs were included in the study. Best overall response to chemotherapy was complete remission in 80 dogs (81.6%) and partial remission in 18 dogs (18.4%). Median progression-free survival (PFS) for the entire population was 252 days (range 19-1068). Factors significantly associated with achieving partial (rather than complete) remission following CHOP included presence of thrombocytopenia at diagnosis (OR 6.88; 95% CI 1.98-23.93; P = .002), baseline serum globulin concentration (OR 2.63; 95% CI 1.03-6.75; P = .044), and age at diagnosis (OR 1.36; 95% CI 1.08-1.71; P = .009). Factors significantly associated with PFS in the lowest quartile (≤93 days) included presence of thrombocytopenia at diagnosis (OR 8.72; 95% CI 1.54-49.33; P = .014), age at diagnosis (OR 1.47; 95% CI 1.12-1.94; P = .005), and baseline neutrophil count (OR 1.18; 95% CI 1.02-1.37; P = .025). Presence of thrombocytopenia, greater age, higher neutrophil count, and higher serum globulin concentration all may be associated with a particularly poor outcome in dogs receiving CHOP-based chemotherapy for DLBCL.

Retrospective comparison of three doses of metronomic chlorambucil for tolerability and efficacy in dogs with spontaneous cancer.

The study hypothesis is that higher doses of metronomic (low-dose) chlorambucil will improve outcome without significantly worsening adverse events (AE). Retrospectively, 88 dogs were screened to assess for tolerability and response to chlorambucil utilizing retrospective and prospective data sets, comparing metronomic oral daily doses 4, 6 and 8 mg m2 . There were 78 and 70 dogs in the tolerability and efficacy portions, respectively. The severity of gastrointestinal (GI) AE was significantly worse, and time to development of GI events was significantly shorter at 6 mg m2 than at 4 mg m2 (both P < 0.001). Chlorambucil was discontinued earlier in the dogs treated at the 6 mg m2 doses than in the dogs treated at 4 mg m2 (P = 0.015). Thrombocytopenia occurred significantly earlier at 8 mg m2 than at 4 mg m2 (P = 0.017). Higher doses of metronomic (low-dose) chlorambucil did not provide improved responses and were associated with more AE.

Risk factors for treatment-related adverse events in cancer-bearing dogs receiving piroxicam.

Piroxicam has antitumour effects in dogs with cancer, although side effects may limit its use. The purpose of this study was to retrospectively identify factors predisposing cancer-bearing dogs to adverse events (AEs) following piroxicam therapy. Medical records of dogs presented to the Purdue Veterinary Teaching Hospital between 2005 and 2015 were reviewed, and 137 dogs met the criteria for study inclusion. Toxic effects of piroxicam in these dogs were graded according to an established system. Multivariate logistic regression was used to estimate the extent to which certain factors affected the risk for AEs. Age [odds ratio (OR) 1.250, P = 0.009; 95% confidence interval (CI) 1.057-1.479] and concurrent use of gastroprotectant medications (OR 2.612, P = 0.025; 95% CI 1.127-6.056) significantly increased the risk for gastrointestinal AEs. The results of this study may help inform the risk versus benefit calculation for clinicians considering the use of piroxicam to treat dogs with cancer.

Inter- and intra-rater reliability of calliper-based lymph node measurement in dogs with peripheral nodal lymphomas.

The purpose of this study was to assess reliability of lymph node measurements between and within raters in dogs with nodal lymphomas. Three raters measured lymph nodes from 20 dogs twice prior to and once after administering chemotherapy. Sum tumour volume (TV) and sum longest diameter (LD) of all lymph nodes at each time point, and the percent change in measurements following chemotherapy, were calculated for each dog. Inter- and intra-rater reliability were assessed with the intraclass correlation coefficient (ICC). ICC for inter-rater sum TV and sum LD prior to chemotherapy were 0.86 and 0.80, respectively. ICC for inter-rater sum TV and sum LD after chemotherapy were 0.95 and 0.91, respectively. ICC for percent change in sum TV and sum LD were 0.96 and 0.94, respectively. ICC for intra-rater reliability ranged from 0.90 to 0.98 for each rater. Inter- and intra-rater reliability in measurements among the three raters was good to excellent.

Predictive value of ex vivo biodynamic imaging in determining response to chemotherapy in dogs with spontaneous non-Hodgkin's lymphomas: a preliminary study.

Biodynamic imaging (BDI) is a novel phenotypic cancer profiling technology which optically characterizes changes in subcellular motion within living tumor tissue samples in response to ex vivo treatment with cancer chemotherapy drugs. The purpose of this preliminary study was to assess the ability of ex vivo BDI to predict in vivo clinical response to chemotherapy in ten dogs with naturally-occurring non-Hodgkin's lymphomas. Pre-treatment tumor biopsy samples were obtained from all dogs and treated ex vivo with doxorubicin (10 µM). BDI measured six dynamic biomarkers of subcellular motion from all biopsy samples at baseline and at regular intervals for 9 h following drug application. All dogs subsequently received doxorubicin to treat their lymphomas. Best overall response to and progression-free survival time following chemotherapy were recorded for all dogs. Receiver operating characteristic (ROC) curves were used to determine accuracy and identify possible cut-off values for the BDI-measured biomarkers which could accurately predict those dogs' cancers that would and would not respond to doxorubicin chemotherapy. One biomarker (designated 'MEM') showed 100% discriminative capability for predicting clinical response to doxorubicin (area under the ROC curve = 1.00, 95% CI 0.692-1.000), while other biomarkers also showed promising predictive capability. These preliminary findings suggest that ex vivo BDI can accurately predict treatment outcome following doxorubicin chemotherapy in a spontaneous animal cancer model, and is worthy of further investigation as a technology for personalized cancer medicine.

Immunohistochemical characterization of feline mast cell tumors.

Expression of histamine, serotonin, and KIT was evaluated in 61 archived feline mast cell tumors (MCTs) from the skin (n = 29), spleen (n = 17), and gastrointestinal (GI) tract (n = 15) using immunohistochemistry. Twenty-eight percent of cutaneous MCTs, 18% of splenic MCTs, and 53% of GI MCTs displayed histamine immunoreactivity. Serotonin immunoreactivity was detected in 3 GI and 1 cutaneous MCT. Sixty-nine percent of cutaneous MCTs, 35% of splenic MCTs, and 33% of GI MCTs were positive for KIT. Expression of these biogenic amines and KIT was less common than expected. Results of this study suggest heterogeneity in feline MCTs based on anatomic location. Further studies are needed to explain the significance of these differences.

Prospective trial of metronomic chlorambucil chemotherapy in dogs with naturally occurring cancer.

The purpose of this study was to assess the toxicoses and antitumor activity of metronomic chlorambucil at a dosage of 4 mg m(-2) daily in dogs with naturally occurring cancer. Thirty-six dogs were enrolled in the study. The protocol was well tolerated with no grade 3 or 4 toxicoses noted. Complete remission was achieved, and lasted over 35 weeks in three dogs (mast cell tumour, soft tissue sarcoma and thyroid carcinoma). Partial remission was noted in 1 dog with histiocytic sarcoma (39 weeks duration) for an overall remission rate of 11% (4 of 36). Stable disease was noted in 17 dogs (47%) with various other cancers. The median progression-free interval was 61 days, and the median survival time was 153 days. Chlorambucil given in a metronomic protocol showed antitumor activity in dogs with a variety of naturally occurring cancers.

Clinical trial of vinblastine in dogs with transitional cell carcinoma of the urinary bladder.

BACKGROUND: Transitional cell carcinoma (TCC) of the urinary bladder of dogs can be a difficult cancer to treat, and effective therapies are limited. Vinblastine has been used in humans with TCC and has potent anti-proliferative effects against canine TCC cells in vitro. OBJECTIVES: To determine the antitumor activity and toxicoses of vinblastine in dogs with urinary bladder TCC. ANIMALS: Animals selected were 28 privately owned dogs that presented to the Purdue University Veterinary Teaching Hospital (PUVTH) with measurable, histologically confirmed TCC. METHODS: Prospective clinical trial: The starting vinblastine dosage was 3.0 mg/m(2) i.v. every 2 weeks. Treatment continued until cancer progression or unacceptable toxicoses occurred. Complete evaluations (physical exam, complete blood count [CBC], serum biochemical profile, urinalysis, thoracic radiography, abdominal ultrasound [US]) were performed at 8-week intervals. Urinary tract US with bladder tumor mapping was performed monthly. Toxicoses were graded according to Veterinary Co-Operative Oncology Group (VCOG) criteria. RESULTS: Tumor responses included 10 (36%) partial remission, 14 (50%) stable disease, and 4 (14%) progressive disease. The median progression free interval was 122 days (range, 28-399 days). The median survival time was 147 days (range, 28-476 days) from 1st vinblastine treatment to death and 299 days (range, 43-921 days) from diagnosis to death. The majority of dogs (27 of 28) did not have clinically relevant adverse effects. Seventeen of 28 (61%) dogs required dosage reductions because of neutropenia. CONCLUSION AND CLINICAL IMPORTANCE: Vinblastine has antitumor activity against TCC in dogs and can be considered another treatment option for this cancer.

Mechlorethamine, procarbazine and prednisone for the treatment of resistant lymphoma in dogs.

Forty-one dogs with resistant lymphoma were treated with a modified MOPP (mechlorethamine, vincristine, procarbazine and prednisone) protocol (MPP [mechlorethamine, procarbazine and prednisone] administered on a 21-day cycle, shortened from the 28-day MOPP cycle). The overall response rate to MPP was 34% for a median of 56 days (95% confidence interval 30-238). Seventeen percent of dogs had a complete response for a median duration of 238 days, 17% had a partial response for a median of 56 days and 32% had stable disease for a median of 24 days. Histological grade or cell morphology on cytology was associated with response. Minimal toxicity was observed with the MPP protocol, suggesting that further dose intensification or addition of another chemotherapeutic agent would be possible.