Carboplatin and piroxicam therapy in 31 dogs with transitional cell carcinoma of the urinary bladder

Invasive transitional cell carcinoma (TCC) of the urinary bladder responds poorly to medical therapy. Combining platinum chemotherapy with a cyclooxygenase (cox) inhibitor has shown promise against canine TCC, where the disease closely mimics the human condition. A phase II clinical trial of carboplatin combined with the cox inhibitor, piroxicam, was performed in 31 dogs with naturally occurring, histopathologically confirmed, measurable TCC. Complete tumour staging was performed before and at 6‐week intervals during therapy. Tumour responses in 29 dogs included 11 partial remissions, 13 stable disease and five progressive disease. Two of the 31 dogs were withdrawn prior to the re‐staging of the tumour. Gastrointestinal toxicity was observed in 23 dogs. Hematologic toxicity was noted in 11 dogs. The median survival was 161 days from first carboplatin treatment to death. In conclusion, carboplatin/piroxicam induced remission in 40% of dogs providing evidence that a cox inhibitor enhances the antitumour activity of carboplatin. The frequent toxicity and limited survival, however, do not support the use of this specific protocol against TCC.     

Evaluation of microsatellite instability in urine for the diagnosis of transitional cell carcinoma of the lower urinary tract in dogs

Background: The accumulation of frame‐shift mutations in microsatellites (MS), termed microsatellite instability (MSI), is associated with certain tumors. MSI and its detection in urine samples has been used to aid in the detection of human bladder cancer. Hypothesis: Evaluation of MSI in urine is a useful assay test for diagnosis of transitional cell carcinoma (TCC) in dogs and is more specific than the commercially available, veterinary bladder tumor analyte (V‐BTA) test. Animals: Seventy‐three dogs: healthy controls (n= 21), proteinuric (n= 12), lower urinary tract disease excluding TCC (n= 17), and TCC (n= 23). Methods: Prospective observational study. Urine samples collected from each animal were evaluated for MSI and using the V‐BTA. For MSI detection, 22 MS sequences were polymerase chain reaction amplified from urine and blood, subjected to capillary electrophoresis, and the MS genotypes were compared. Aberration in ≥15% of MS was considered indicative of MSI. Results: MSI was detected in 11 of 23 (48%) urine samples from dogs with TCC. MSI was also detected in 12 of 50 (24%) of the control animals, including 29, 16, and 24% of healthy, proteinuric, and lower urinary disease dogs, respectively. In this population, sensitivity and specificity of MSI analysis was 48 and 76%, respectively, compared with 83 and 64%, respectively, for the V‐BTA test. Conclusions: MS analysis as performed in this study is not useful in the diagnosis of TCC.     

Evaluation of cisplatin administered with piroxicam in dogs with transitional cell carcinoma of the urinary bladder

OBJECTIVE: To evaluate the antitumor activity and toxic effects of a conservative dose of cisplatin administered in combination with piroxicam to dogs with transitional cell carcinoma (TCC) of the urinary bladder. DESIGN: Clinical trial (nonrandomized, noncontrolled). ANIMALS: 14 client-owned dogs with histologically confirmed TCC of the urinary bladder. PROCEDURES: Each dog was treated with cisplatin (50 mg/m(2), i.v., q 21 d [reduced to 40 mg/m(2), i.v., q 21 d because of toxic effects]) and piroxicam (0.3 mg/kg [0.14 mg/lb], PO, q 24 h). A CBC, serum biochemical analyses, and urinalysis were performed prior to each cisplatin treatment. Tumor staging (determined from thoracic and abdominal radiographic and urinary bladder ultrasonographic findings) was performed before treatment and at 6-week intervals during treatment. RESULTS: 5 dogs received only 1 dose of cisplatin because of the rapid progression of disease (n = 2) or toxic effects (3). With regard to the neoplastic disease among the other 9 dogs, 1 had partial remission, 5 had stable disease, and 3 had progressive disease after 6 weeks of treatment. Median progression-free interval was 78 days (range, 20 to 112 days). Median survival time was 307 days (range, 29 to 929 days). Moderate to severe renal toxicosis and moderate to severe gastrointestinal toxicosis developed in 5 and 8 dogs, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Because of minimal efficacy and associated renal and gastrointestinal toxicosis, administration of cisplatin (40 to 50 mg/m(2)) with piroxicam cannot be recommended for treatment of dogs with TCC of the urinary bladder.     

Expression of cyclooxygenase-2 in transitional cell carcinoma of the urinary bladder in dogs

OBJECTIVE: To evaluate expression of cyclooxygenase (COX)-1 and COX-2 in the urinary bladder epithelium of clinically normal dogs and in transitional cell carcinoma cells of dogs. ANIMALS: 21 dogs with transitional cell carcinoma of the urinary bladder and 8 dogs with clinically normal urinary bladders. PROCEDURE: COX-1 and COX-2 were evaluated by use of isoform-specific antibodies with standard immunohistochemical methods. RESULT: COX-1, but not COX-2, was constitutively expressed in normal urinary bladder epithelium; however, COX-2 was expressed in neoplastic epithelium in primary tumors and in metastatic lesions of all 21 dogs and in new proliferating blood vessels in 3 dogs. Also, COX-1 was expressed in the neoplastic cells. CONCLUSIONS AND CLINICAL RELEVANCE: Lack of expression of COX-2 in normal bladder epithelium and its substantial expression in transitional cell carcinoma cells suggest that this isoform may be involved in tumor cell growth. Inhibition of COX-2 is a likely mechanism of the antineoplastic effects of non steroidal antiinflammatory drugs.     

Antitumor effects of deracoxib treatment in 26 dogs with transitional cell carcinoma of the urinary bladder

OBJECTIVE-To evaluate the antitumor activity and toxic effects of deracoxib, a selective cyclooxygenase-2 inhibitor, in dogs with transitional cell carcinoma (TCC) of the urinary bladder. DESIGN-Clinical trial. Animals-26 client-owned dogs with naturally occurring, histologically confirmed, measurableTCC of the urinary bladder. PROCEDURES-Dogs were treated PO with deracoxib at a dosage of 3 mg/kg/d (1.36 mg/lb/d) as a single-agent treatment for TCC. Tumor response was assessed via radiography, abdominal ultrasonography, and ultrasonographic mapping of urinary bladder masses. Toxic effects of deracoxib administration in dogs were assessed through clinical observations and hematologic and biochemical analyses. RESULTS-Of 24 dogs for which tumor response was assessed, 4 (17%) had partial remission, 17 (71%) had stable disease, and 3 (13%) had progressive disease; initial response could not be assessed in 2 of 26 dogs. The median survival time was 323 days. Median time to progressive disease was 133 days. Renal, hepatic, and gastrointestinal abnormalities attributed to deracoxib administration were noted in 4% (1/26), 4% (1/26), and 19% (5/26) of dogs, respectively. CONCLUSIONS AND CLINICAL RELEVANCE-Results indicated that deracoxib was generally well tolerated by dogs and had antitumor activity against TCC.     

Evaluation of a bladder tumor antigen test as a screening test for transitional cell carcinoma of the lower urinary tract in dogs

OBJECTIVE: To evaluate the veterinary version of the bladder tumor antigen (V-BTA) test as a screening test for transitional cell carcinoma (TCC) of the lower urinary tract of dogs. ANIMALS: 229 client-owned dogs. PROCEDURE: Urine samples from dogs were shipped overnight to a single laboratory to facilitate testing within 48 hours of collection by use of the V-BTA rapid latex agglutination urine dipstick test. Groups of dogs included the following: 1) dogs with TCC of the lower urinary tract, 2) healthy control dogs, 3) unhealthy control dogs with non-TCC urinary tract disease, and 4) unhealthy control dogs without urinary tract disease. Test sensitivity and specificity were calculated by use of standard methods. Logistic models were developed to assess the effect of disease status, test conditions, urine composition, and signalment on the performance of the V-BTA test. RESULTS: A total of 229 urine samples were analyzed, including 48 from dogs with suspected (n = 3) or confirmed (45) TCC. Test sensitivities were 88, 87, and 85% for all dogs with (suspected and confirmed) TCC, dogs with confirmed TCC at any site, and dogs with confirmed TCC of the urinary bladder, respectively. Test specificities were 84, 41, and 86% for healthy control dogs, unhealthy control dogs with non-TCC urinary tract disease, and unhealthy control dogs without urinary tract disease, respectively. The test performed slightly better on centrifuged urine samples than on uncentrifuged urine samples. CONCLUSIONS AND CLINICAL RELEVANCE: Our results indicate that the V-BTA test is useful in screening for urinary tract TCC in dogs.     

Ureterocolonic anastomosis in a dog with transitional cell carcinoma of the urinary bladder

Ureterocolonic anastomosis and cystectomy were performed in a dog for treatment of transitional cell carcinoma of the urinary bladder. The dog remained an acceptable house pet for 10 months after surgery. However, the tumor recurred 10 months after surgery, and the dog was euthanatized. Our results indicated that the combination of ureterocolonic anastomosis and cystectomy can be an acceptable form of palliative treatment for transitional cell carcinoma of the urinary bladder in the dog.     

Survival analysis in dogs with urinary transitional cell carcinoma that underwent whole‐body computed tomography at diagnosis

This retrospective study aimed to evaluate factors associated with survival and to compare characteristics between tumour localizations in dogs with urinary transitional cell carcinoma (TCC) that underwent whole‐body computed tomography (CT) at diagnosis. Dogs with histologically confirmed TCC that received medical therapy between 2010 and 2017 were included; dogs that underwent surgery or radiotherapy for the primary tumour were excluded. According to the CT findings, primary tumour localization (classified into the Bladder, Urethra and Bladder and Urethra groups), prostate involvement, iliosacral lymphadenomegaly, sternal lymphadenomegaly and metastasis to the bone and lung were evaluated for survival analysis. CT at diagnosis revealed iliosacral lymphadenomegaly, sternal lymphadenomegaly, bone metastasis and lung metastasis in 47.7%, 18.5%, 24.6% and 35.4% of the 65 included dogs, respectively. The overall median survival time was 196 days. On multivariable analysis, TCC localization (hazard ratio [HR], 1.90; P = .037), bone metastasis (HR, 2.76; P = .013) and sternal lymphadenomegaly (HR, 3.56; P = .004) were significantly associated with survival. Compared to the Bladder group (n = 16), the Urethra group (n = 26) had higher metastasis rates to the bone (6.3% vs 42.3%; P = .045) and lung (6.3% vs 46.2%; P = .022). The survival time was shorter in the Urethra group than in the Bladder group (121.5 vs 420 days; P < .001), and it was similar only in female dogs (247 vs 420 days; P = .031). These findings suggest that whole‐body CT could be valuable for predicting the prognosis in urinary TCC.     

Vinorelbine rescue therapy for dogs with primary urinary bladder carcinoma

The goal of this study was to evaluate the anti‐tumour activity and toxicoses of vinorelbine as a palliative rescue therapy for dogs with primary urinary bladder carcinoma. Thirteen dogs refractory to prior chemotherapeutics and one dog naïve to chemotherapeutic treatment were enrolled. Vinorelbine (15 mg m^?2 IV) was administered intravenously along with concurrent oral anti‐inflammatory drugs, if tolerated. A median of six doses of vinorelbine (range: 1–16) was administered. Two dogs (14%) had partial responses, and eight (57%) experienced stable disease. Subjective improvement in clinical signs was noted in 11 dogs (78%). Adverse events were mild and primarily haematological in nature. Median time to progression was 93 days (range: 20–239 days). Median survival time for all dogs was 187 days; median survival for 13 pre‐treated dogs was 207 days. Vinorelbine may have utility in the management of canine primary urinary bladder carcinoma and should be evaluated in a prospective study.     

Hypofractionated radiation therapy for the treatment of malignant melanoma and squamous cell carcinoma in dogs and cats

This study describes the experience with hypofractionated radiation therapy of squamous cell carcinoma and melanoma in dogs and cats. A total dose of 32-48 Gray (Gy) was delivered once a week in 8 Gy fractions. 34 animals in which a complete surgical excision was impossible were treated. There was no tumor detectable macroscopically in 14 patients at the beginning of radiation therapy. In 20 animals the median volume of the tumor was 9.9 cm3. The median survival times and the local tumor control of squamous cell carcinoma of the oral and nasal cavities and of the body are comparable to results which were reached with a Monday-Wednesday-Friday scheme. For the treatment of Melanoma the hypofractionated radiation therapy is first choice. There are no significant side effects. Late side effects did not occur. 88% of the owners are satisfied with this kind of treatment and would choose it again.