CT characteristics of uterine and vaginal mesenchymal tumours in dogs.

OBJECTIVES: To describe the CT characteristics of uterine and vaginal mesenchymal tumours in dogs and to discuss imaging findings of the tumour types encountered. MATERIALS AND METHODS: Retrospective study on female dogs with confirmed histological diagnosis of uterine and vaginal mesenchymal tumours and available CT images. RESULTS: 120 records obtained through a medical record search were manually evaluated for eligibility, and 11 dogs presenting masses associated with the genital tract were identified. Of these 11 dogs, 7 dogs met the inclusion criteria and were included in the study. A clear degree of overlap was present between measurements of maximal diameter of benign and malignant tumours; however, malignant neoplasms tended to occupy a larger portion of the pelvic canal. Objective measurements of length suggest that malignant tumours were longer than benign forms. Bone involvement was only observed with malignancy. CLINICAL SIGNIFICANCE: Although CT is likely to play a limited role in the advanced workup of uterine and vaginal mesenchymal neoplasms, CT may represent a more accessible diagnostic tool than MRI and results of this study may help imagers familiarise themselves with their appearances.

Prevalence of proteinuria in a canine oncology population.

OBJECTIVE: To evaluate the point prevalence of proteinuria in dogs presenting to the University of Georgia Oncology Service for the first time. MATERIALS AND METHODS: In this prospective study, 60 client-owned dogs with a confirmed cancer diagnosis were included but those with lower urinary tract neoplasia were excluded. Each dog's signalment, cancer diagnosis, previous cancer treatments, current medications and travel history were recorded. Renal values, electrolytes, packed cell volume, total solids, systolic blood pressure, urinalysis, urine protein:urine creatinine and retinal examinations were recorded. Non-proteinuric, borderline proteinuria and overt proteinuria were defined as urine protein:urine creatinine <0·2, ≥0·2 but <0·5, and ≥0·5, respectively. Urine culture was performed in dogs with active urine sediments or overt proteinuria. RESULTS: Twenty-nine dogs were non-proteinuric (48·3%), 22 (36·7%) borderline proteinuric and nine (15%) overtly proteinuric. None were azotaemic. Hypertension (systolic blood pressure ≥160 mmHg) was detected in 18 (30%) dogs. Of these, six were non-proteinuric, nine borderline proteinuric, and three overtly proteinuric. Proteinuria was detected in 51% of dogs presented to our oncology service, the majority of which were classified as borderline. CLINICAL SIGNIFICANCE: The high proportion of proteinuria in dogs in this study suggests that screening for proteinuria in dogs with cancer may be prudent. Larger studies are required to correlate specific cancer types and the impact of treatment with the development, magnitude and persistence of proteinuria.

Rabacfosadine for relapsed canine B-cell lymphoma: Efficacy and adverse event profiles of 2 different doses.

Rabacfosadine (RAB), a novel double prodrug of the acyclic nucleotide phosphonate PMEG, preferentially targets neoplastic lymphocytes with reduced off target toxicity. Historical studies have suggested that every 21-day dosing is effective with acceptable toxicity. The purpose of this study was to evaluate RAB's safety and efficacy at 2 different doses every 21 days in dogs with relapsed B-cell lymphoma. Dogs that had failed 1 doxorubicin-based chemotherapy protocol were eligible for inclusion in this prospective trial. Once enrolled, dogs were randomized to receive RAB at either 0.82 mg/kg or 1.0 mg/kg as a 30-minute IV infusion every 21 days for up to 5 treatments. Response assessment and adverse event (AE) evaluation were performed every 21 days via VCOG criteria. Fifty dogs were enrolled, with 16 treated at 0.82 mg/kg and 34 treated at 1.0 mg/kg. The overall response rate was 74%, with 45% of dogs experiencing a complete response (CR). The median progression free intervals (PFIs) were 108 days, 172 days and 203 days for all dogs, all responders, and all CRs, respectively. Response rates and PFIs were similar in both treatment groups. The incidence of AEs, dose delays, dose reductions and withdrawals were not statistically different between the 2 groups. The AEs observed were similar to those previously reported and included hematologic, gastrointestinal, dermatologic and pulmonary AEs. One dog had grade 5 pulmonary fibrosis; otherwise, AEs resolved with supportive treatment. Rabacfosadine is a generally well tolerated, effective chemotherapy option for dogs with relapsed B-cell lymphoma.

Phase II evaluation of VDC-1101 in canine cutaneous T-cell lymphoma.

BACKGROUND: Canine cutaneous T-cell lymphoma (CTCL) is an uncommon disease for which efficacious therapies are lacking. The novel anticancer nucleotide prodrug VDC-1101 (formerly known as GS-9219) has shown efficacy in dogs with multicentric lymphoma. One of the observed adverse effects with this drug was a skin change characterized by hair loss, erythema, and pruritus, implying delivery of VDC-1101 to the skin. HYPOTHESIS/OBJECTIVES: The primary study objective was to identify the objective response rate (ORR) to VDC-1101 in canine CTCL; secondary objectives included characterization of progression-free survival (PFS) and adverse events (AEs). ANIMALS: Twelve dogs with chemotherapy-naïve or relapsed, histologically and immunohistochemically confirmed CTCL. METHODS: Dogs received VDC-1101 as a 30-minute IV infusion once every 21 days. Prednisone (1 mg/kg PO q48h) was administered concurrently. RESULTS: In 11 evaluable patients, responses included 1 complete response (CR), 4 partial responses (PR), 2 stable disease (SD), and 4 progressive disease for an ORR of 45% and biologic response rate (CR/PR/SD) of 64%. The median PFS was 37.5 days (26 to >399 days), which includes 1 durable and ongoing CR (>1 year). Gastrointestinal and hematologic AEs were mild; no dogs developed grade 3 or 4 AEs. Three dogs developed dermatopathies and 1 of these dogs was removed from the study as a result of this AE. CONCLUSIONS AND CLINICAL IMPORTANCE: VDC-1101 has activity against canine CTCL and could provide another treatment option in a disease process with a poor prognosis.

Indirect assessment of dihydropyrimidine dehydrogenase activity in cats.

Use of 5-fluoropyridimine antimetabolite drugs, specifically 5-fluorouracil (5-FU), has been discouraged in cats because of adverse events including neurotoxicity and death. Causes of toxicity have never been elucidated. In humans, toxicity has been associated with ineffective metabolism secondary to deficiencies in dihydropyrimidine dehydrogenase (DPD). Direct assessment of DPD activity is challenging; determination of uracil:dihydrouracil (U:UH2 ) in plasma using high performance liquid chromatography (HPLC) has been reported as an indirect measurement. U:UH2 was measured in the plasma of 73 cats. Mean U:UH2 for all cats was 1.66 ± 0.11 (median 1.53, range 0.24-7.00). Seventeen (23%) cats had U:UH2 >2, a value associated with decreased DPD activity in humans. Spayed female cats had significantly lower U:UH2 as compared with intact females, and age and U:UH2 were weakly but significantly negatively correlated (r = -0.26). Studies correlating U:UH2 and 5-FU tolerability are required to further determine the validity and use of this test in cats.

Phase I clinical trial of vinorelbine in tumor-bearing cats.

BACKGROUND: Vinorelbine (VRL) has been investigated in dogs, but its use in cats has not been studied. HYPOTHESIS/OBJECTIVES: To determine the maximal tolerated dose (MTD) and dose-limiting toxicity (DLT) of VRL in tumor-bearing cats. ANIMALS: Cats were included in this prospective phase I trial if they had confirmed malignancy, received ≥1 VRL treatment, and had adequate follow-up. Previous treatment was acceptable, but concurrent chemotherapy or radiotherapy was not permitted. METHODS: Using a modified phase I design, cats were enrolled in cohorts of 3 at a starting dosage of 9 mg/m(2) . Cats tolerating the first treatment well were eligible to receive additional VRL treatments at escalating dosages; escalations beyond the perceived MTD were permitted based on individual tolerance. Intended treatment interval was 7 days. Patient histories, physical examinations, and complete blood counts were performed weekly. RESULTS: Nineteen cats were included. Sixty-one VRL treatments were administered. Median number of treatments was 2 (range, 1-9). Starting dosages were 9-12 mg/m(2) . Maximal dosage administered was 15.5 mg/m(2) . The MTD was 11.5 mg/m(2) . Acute DLTs were neutropenia, vomiting, and nephrotoxicity. Other notable toxicities were weight loss and anemia. CONCLUSIONS AND CLINICAL IMPORTANCE: Vinorelbine is tolerated in cats at a weekly interval. Recommended starting dosage is 11.5 mg/m(2) . Neutropenia was transient, lasting <7 days; vomiting was self-limiting in most cases. Although VRL-associated nephrotoxicity has not been reported, potential attribution of this toxicity to VRL must not be discounted. Further investigation of the efficacy of VRL in feline malignancies is warranted.

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.

Phase II clinical evaluation of lomustine chemotherapy for feline vaccine-associated sarcoma.

Treatment of feline vaccine-associated sarcoma (VAS) is challenging, in part due to the high likelihood of tumour recurrence despite aggressive local therapy. Lomustine is potentially an attractive agent to add to the current treatment armamentarium. In this de-escalating phase I/II prospective trial, 28 cats with measurable VAS were treated at target dosages of 38-60 mg m(-2) every 3 weeks until disease progression. The overall response rate was 25%, with a median progression-free survival and median duration of response of 60.5 and 82.5 days, respectively. Haematologic toxicity, specifically cumulative neutropenia, was significant, and dose reductions and treatment delays were common. Although these data support further investigation of lomustine for the treatment of VAS, safe, multidosing protocols must first be determined.

Outcome of 19 dogs with parathyroid carcinoma after surgical excision.

Parathyroid carcinoma (PTC) is rare in dogs and there is little information documenting its treatment and prognosis. The objective of this study was to describe the outcome of dogs with PTC treated with surgical excision. Medical records of 19 dogs undergoing surgical excision of PTC between 1990 and 2010 were reviewed retrospectively. Dogs were presented for clinical hypercalcaemia or incidental hypercalcaemia noted by referring veterinarians on routine serum chemistry profiles. A parathyroid nodule was identified with cervical ultrasound in 17/17 dogs. Hypercalcaemia resolved in 18/19 dogs within 4 days postoperatively. Nine developed hypocalcaemia. None were confirmed to develop recurrent or metastatic PTC. The only death associated with PTC was a dog that was euthanized for intractable hypocalcaemia 9 days after surgery. Estimated 1-, 2- and 3-year survival rates were 72, 37 and 30%, respectively. Excision of PTC results in resolution of hypercalcaemia and excellent tumour control.

5-Lipoxygenase expression in benign and malignant canine prostate tissues.

5-Lipoxygenase (5-LO) is overexpressed in human prostate carcinomas (PCs), and its inhibition decreases proliferation and induces apoptosis in prostate cancer cell lines. We hypothesized that 5-LO would be overexpressed in canine PC compared with benign prostate tissue and may be important in the pathogenesis of the disease. Immunoblot analysis of canine PC and benign prostatic hyperplasia (BPH) tissues demonstrated 5-LO expression in both. 5-LO immunohistochemical staining was not significantly different within the stromal or epithelial components of canine primary PC, BPH or suppurative prostatitis, suggesting that differential expression of this enzyme does not occur in these conditions. The percentage of tumour cells expressing 5-LO was significantly lower in metastatic PC lesions compared with primary PC (P < 0.0001). This decreased expression may indicate down-regulation or altered expression of the enzyme with progression of canine PC to a metastatic phenotype.

Combination chemotherapy with continuous L-asparaginase, lomustine, and prednisone for relapsed canine lymphoma.

BACKGROUND: The combination of lomustine, L-asparaginase, and prednisone (LAP) is an effective rescue treatment for canine lymphoma (LSA). In a previous study, we reported that remission was typically lost around the time L-asparaginase was discontinued. HYPOTHESIS: Use of L-asparaginase with each lomustine treatment will be well tolerated and efficacious as a rescue therapy for canine LSA. ANIMALS: Forty-eight client-owned dogs with cytologically confirmed multicentric LSA whose disease had relapsed after a cyclophosphamide, doxorubicin, vincristine, and prednisone-based chemotherapy protocol were included. METHODS: Lomustine was administered orally at 3-week intervals, concurrently with subcutaneous or intramuscular L-asparaginase for a total of 5 doses or until disease progression. Prednisone was administered at a tapering dose for the duration of the protocol. RESULTS: The overall response rate (ORR) for dogs treated with this protocol was 77%, with 65% achieving a complete response (CR). The median time to progression (TTP) was 70 days. Based on loose comparison, these findings are not significantly different from our previously reported historical control. The actual CCNU dosage administered did not affect response rate or remission duration. CONCLUSIONS/CLINICAL IMPORTANCE: These findings support previous data concluding that the LAP protocol is a viable rescue treatment option for dogs with LSA. However, results from this study suggest that continued use of L-asparaginase with each lomustine treatment does not significantly increase remission duration and toxicity appears greater.

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.