Early Tumor Response to Intraarterial or Intravenous Administration of Carboplatin to Treat Naturally Occurring Lower Urinary Tract Carcinoma in Dogs

Background

Survival times and tumor responses associated with malignant neoplasia of the lower urinary tract are poor despite the vast array of current treatments. Therefore, the evaluation of alternative treatments, such as intraarterial administration of chemotherapy (IAC) should be considered.

Objective

To describe a technique for superselective catheterization for IAC and to evaluate initial tumor response by ultrasonography after both IAC and intravenous administration of chemotherapy (IVC).

Animals

Client‐owned dogs with lower urinary tract neoplasia treated with either IVC (n = 15) or IAC (n = 11).

Methods

Retrospective study. An arterial approach via the carotid or femoral artery was utilized to obtain superselective access and administer chemotherapy in the IAC cases. Medical record review was performed, data were recorded, and recorded variables were evaluated statistically.

Results

Intraarterial chemotherapy was successfully administered in all cases. There was a significantly greater decrease in longest unidimensional measurement in the IAC group as compared to the IVC group (P = .013). The IAC group was also significantly more likely to have a tumor response as assessed by modified RECIST guidelines (P = .049). Dogs in the IAC group were significantly less likely to develop anemia (P = .001), lethargy (P = .010) and anorexia (P = .024).

Conclusion and Clinical Importance

This study demonstrated the feasibility and efficacy of performing IAC for lower urinary tract neoplasia. Further investigation is necessary as the follow‐up time was short and the impact on long‐term outcome and survival was not determined.     

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.     

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 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.     

Transitional cell carcinoma of the urinary bladder in a 12‐year‐old Belgian Warmblood gelding

A 12‐year‐old Belgian Warmblood gelding was examined for haematuria and dysuria of 24 h duration. Cystoscopy revealed an intraluminal multinodular soft tissue mass originating from the dorsal bladder neck. Histopathological examination of biopsies identified transitional cell carcinoma. The bladder mass was surgically debulked via a temporary perineal urethrotomy. The horse commenced treatment with oral piroxicam. Follow‐up examination 18 months post operatively revealed no evidence of tumour recurrence. Neoplasia of the equine bladder is uncommon and this case describes the successful short‐term outcome of treatment of a transitional cell carcinoma by surgical debulking and oral piroxicam.     

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.     

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.     

Superficial corneal squamous cell carcinoma occurring in dogs with chronic keratitis

Objective Canine corneal squamous cell carcinoma (SCC) is a rare tumor, with only eight cases previously published in the veterinary literature. The Comparative Ocular Pathology Lab of Wisconsin (COPLOW) has diagnosed 26 spontaneously occurring cases, 23 in the past 4 years. This retrospective study describes age and breed prevalence, concurrent therapy, biologic behavior, tumor size and character, and 6‐month survival rates after diagnosis. Results A search of the COPLOW database identified 26 corneal SCC cases diagnosed from 1978 to 2008. There is a strong breed predilection (77%) in brachycephalic breeds, particularly those prone to keratoconjunctivitis sicca. The mean age was 9.6 years (range 6–14.5 years). Follow‐up information >6 months was available for 15 of 26 cases. Recurrence occurred in the same eye in nine cases, seven of which were incompletely excised at the time of first keratectomy. No cases were known to have tumor growth in the contralateral eye and no cases of distant metastases are known. Where drug history is known, 16 of 21 dogs had a history of treatment with topical immunosuppressive therapy (cyclosporine or tacrolimus) at the time of diagnosis. Conclusion Chronic inflammatory conditions of the cornea and topical immunosuppressive therapy may be risk factors for developing primary corneal SCC in dogs. SCC should be considered in any differential diagnosis of corneal proliferative lesions. Superficial keratectomy with complete excision is recommended, and the metastatic potential appears to be low.     

Prognostic factors associated with survival in dogs with lymphocytic-plasmacytic enteritis

Prognostic factors associated with survival in dogs with lymphocytic-plasmacytic enteritis (LPE) were investigated through a retrospective study. Using case records, 48 dogs diagnosed with LPE were classified as survivors (n = 32) or non-survivors (n = 16), and the clinical and clinicopathological parameters were reviewed between the 2 groups by using univariate and multivariate prognostic analysis. Compared to the hospital population, non-survivors had an overrepresentation of the Shiba breed. Results of univariate analysis indicated that anorexia, severe weight loss, packed cell volume, and total protein were significantly associated with survival for 6 months after diagnosis. In multivariate analysis, anorexia and hypoproteinemia were significantly associated with survival. Furthermore, initial response to treatment was strongly associated with poor prognosis. Based on these clinical and laboratory parameters such as anorexia, hypoproteinemia and initial response to treatment, it may be possible to predict poor prognosis in canine LPE.     

Corneal squamous cell carcinoma in two dogs

Purpose To report two cases of corneal squamous cell carcinoma (SCC) in dogs. Methods Corneal tumors were resected by superficial keratectomy in two cases. Immunohistochemistry of the corneal tissues was performed using anti‐p53 antibody. Results The prominent features of the cases were a clinical history of pigmentary keratitis and chronic keratitis. In each case, a corneal mass was surgically removed with a superficial keratectomy and histologically diagnosed as corneal SCC. Both masses were negative for p53. To reduce chronic corneal irritation, 0.1% hyaluronate sodium ophthalmic solution was applied. After more than 15 months of postsurgical follow‐up there has been no recurrence of either neoplasm. Conclusion and discussion Chronic corneal irritation was suspected as the primary etiology for the corneal SCC. Appropriate surgical removal of the mass and subsequent conservative treatment for keratitis provided effective therapy in these two cases.     

Squamous cell carcinoma of the nasal planum in cats and dogs

The purpose of this article is to review the therapeutic options available for the treatment of squamous cell carcinoma of the nasal planum in cats and dogs. The techniques of complete and partial nasal planum resection in the cat are described in detail. Surgical treatment offers the greatest chance of cure, although several options are available for early, less invasive lesions.     

Prognostic factors for dogs with surgically resected gastrointestinal stromal tumors

Few reports have investigated prognosis of canine gastrointestinal stromal tumor (GIST) cases treated by surgical resection alone. In the present study, we investigated the overall survival (OS) and prognostic factors for dogs with GIST treated by surgical complete resection alone. Fifty-three dogs were included, and the median OS was 18 months. Multivariate analysis showed that primary tumors in small intestine (P=0.04) is significantly associated with shorter OS, and median OS of the cases with cecum lesion and those with small intestine lesion was 22 and 6 months, respectively. The present study suggested primary tumor site was a novel prognostic factor for dogs with GIST treated by surgical complete resection alone.     

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.