Transitional cell carcinoma (TCC) is the most common malignancy of the urinary tract in dogs, predominantly affecting older females. Treatment of these tumors is complicated by the fact that up to 20% of these dogs already have metastases at the time of diagnosis. The current paradigm for treating TCC of the urinary tract in dogs has had limited success.
What they did
A clinical trial conducted at the Purdue University Veterinary Teaching Hospital sought to determine the antitumor activity of vinblastine against urinary bladder TCC in dogs. The study group consisted of 28 privately owned dogs, all of which had measurable and histologically confirmed urinary bladder TCC. This group included dogs in which urinary bladder TCC had been newly diagnosed and dogs that had failed to respond to previous therapies.
Initially, all dogs were treated with vinblastine at a dose of 3 mg/m2 given intravenously every two weeks. However, because of marked myelosuppression (neutropenia), especially in dogs weighing less than 33 lb (15 kg), the protocol was modified so that smaller dogs and those that were at risk for a heritable condition that could affect vinblastine metabolism were administered lower initial doses (2.5 mg/m2).
Before each treatment, a complete blood cell count was evaluated. The blood work was repeated monthly, along with a serum chemistry profile, urinalysis, urinary tract ultrasonographic examination, and ultrasound mapping of the bladder masses. Before treatment and at eight-week intervals, thoracic and abdominal radiographic examinations and a full abdominal ultrasonographic examination were performed.
What they found
Complete remission was not achieved in any of the dogs. However, partial remission was observed in 36% of the cases and stable disease in 50%—both of which were considered a beneficial response%—and only 14% were identified to have progressive disease. All the individuals that had failed to respond to previous mitoxantrone treatment exhibited partial remission or stable disease, and 80% of the dogs that had previously failed to respond to cyclooxygenase (COX) inhibitors had a beneficial tumor response while receiving vinblastine. Of the dogs with distant metastatic disease at the beginning of the study, most also had beneficial tumor responses. Furthermore, beneficial tumor responses were associated with an improved progression-free interval (time from first treatment to tumor progression), and partial remission was closely associated with improved survival (start of treatment until death).
Based on the study findings, lower doses of vinblastine are suggested for smaller dogs and those that may be at higher risk for toxicosis. Close monitoring for myelosuppression and appropriate dose adjustments are important for all patients treated with vinblastine. The results of this clinical trial compare favorably to those of traditional therapies and suggest that vinblastine may be a useful option for the treating TCC in dogs. There is also evidence that vinblastine may be effective in cases in which other chemotherapies have failed. Further research to determine whether there are synergistic combinations that can improve response is needed.
Arnold EJ, Childress MO, Fourez LM, et al. Clinical trial of vinblastine in dogs with transitional cell carcinoma of the urinary bladder. J Vet Intern Med 2011;25(6):1385-1390.
Link to abstract: http://onlinelibrary.wiley.com/doi/10.1111/j.1939-1676.2011.00796.x/abstract