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

Abstract

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 Two of the 31 dogs were withdrawn prior to the re-staging of the tumour.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.

Randomized Phase III Trial of Piroxicam in Combination with Mitoxantrone or Carboplatin for First‐Line Treatment of Urogenital Tract Transitional Cell Carcinoma in Dogs

“…Most patients that experienced high‐grade neutropenia were asymptomatic and recovered without intervention other than prophylactic antibiotics. Gastrointestinal toxicosis was far less common in the carboplatin‐treated dogs (26%) in this study compared to a previous study where 74% of dogs with TCC receiving the combination of carboplatin and piroxicam developed gastrointestinal toxicosis 15. Similarly, the hospitalization rate in this study was much lower than previously reported.…”

“…Responses to carboplatin and piroxicam have also been noted in dogs that have not responded to other therapies, and the MST in these dogs was 161 days 15. The overall response rate was 38% in that report; however, gastrointestinal toxicosis was high (noted in 74% of dogs), and 25.8% was hospitalized 15. A PFI of 41 days has been reported in dogs treated with carboplatin alone 16.…”

“…Piroxicam combined with mitoxantrone is commonly used for managing TCC in dogs and has a reported response rate of 35%, a median PFI of 194 days, and a MST of 291 days in dogs treated with this combination 14. Responses to carboplatin and piroxicam have also been noted in dogs that have not responded to other therapies, and the MST in these dogs was 161 days 15. The overall response rate was 38% in that report; however, gastrointestinal toxicosis was high (noted in 74% of dogs), and 25.8% was hospitalized 15.…”

“…Reported response of dogs with TCC to piroxicam combined with either mitoxantrone or carboplatin is similar, with overall response rates of 35% and 38%, respectively 14, 15. However, these combinations have not yet been compared in a randomized prospective trial, and it is currently not known whether either drug may provide superior duration of response and thus be indicated as first‐line treatment.…”

Malignant pilomatricoma in a dog with local and distant metastases treated with chemotherapy and bisphosphonates

“…In this dog, toceranib was used as first line due to ease of administration and tolerability, which was important to the owner. Conventional chemotherapy with platinum agents was chosen based on reported efficacy in various types of carcinomas (Boria et al, 2005;Dominguez et al, 2009) as well as metronomic chemotherapy, which has been previously administered to dogs with different solid tumours (Burton et al, 2011;Spugnini et al, 2014), although we were able to achieve only short-lived responses. The dose of bisphosphonates was chosen based on a recent study where dogs treated at 2 mg/kg were found to have lower levels of N-telopeptide in the urine, suggesting a reduction in focal osteolysis, earlier than dogs receiving a dose of 1 mg/kg, although the difference was not statistically significant (Fan et al, 2007).…”