Randomized Trial of Cisplatin versus Firocoxib versus Cisplatin/Firocoxib in Dogs with Transitional Cell Carcinoma of the Urinary Bladder

Abstract

Background: Cisplatin combined with a nonselective cyclooxygenase (cox) inhibitor has potent antitumor activity against transitional cell carcinoma (TCC) in dogs, but this treatment is limited by renal toxicosis. Cox-2 is expressed in TCC, but only in limited sites within the kidney. A cox-2 inhibitor could enhance the antitumor activity of cisplatin with potentially fewer adverse effects on the kidney.Hypothesis: Cisplatin/cox-2 inhibitor treatment will have greater antitumor activity but no more renal toxicosis than cisplatin alone in dogs with TCC.Animals: Forty-four dogs with naturally occurring urinary bladder TCC. Methods: Dogs were randomized to receive cisplatin (60 mg/m 2 IV q21d), firocoxib (5 mg/kg PO q24h), or the combination. Tumor measurements were determined before and at 6-week intervals during treatment. Renal function was monitored by serum creatinine concentration, iohexol clearance, and urine specific gravity. Toxicoses were graded according to Veterinary Co-Operative Oncology Group (VCOG) criteria.Results: The remission rate with cisplatin/firocoxib (57%) was significantly (P = .021) higher than that with cisplatin alone (13%). Renal and gastrointestinal toxicoses were common in dogs receiving cisplatin, but there were no significant differences between dogs receiving cisplatin or cisplatin/firocoxib. Firocoxib alone induced partial remission or stable disease in 20 and 33% of dogs, respectively.Conclusions: Firocoxib significantly enhanced the antitumor activity of cisplatin resulting in partial remission in more than half of the cases. The toxicoses inherent to cisplatin, however, were noted in dogs receiving this combination. Firocoxib had antitumor effects as a single agent and can be considered a palliative treatment for dogs with 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

“…These adverse effects demonstrate the need for monitoring for toxicosis. Other nonsteroidal anti‐inflammatory drugs have been described for the management of TCC and might be considered as alternatives in dogs that do not tolerate piroxicam 32, 33…”

The in Vitro and in Vivo Anti-Cancer Potential of Mycobacterium Cell Wall Fraction (MCWF) Against Canine Transitional Cell Carcinoma of the Urinary Bladder

“…TCC is commonly found in the trigonal location and in more than 50% of dogs involves the urethra which could lead to dysuria and partial or complete obstruction of the urinary tract [10,11]. An additional problem for dogs with TCC are the distant metastases seen in approximately 20% of cases at diagnosis and are associated with poor prognosis [2,11]. Dogs with TCC are also at high risk for the development of secondary urinary tract infections.…”

“…Although medical therapy is not usually curative, remission or stable disease can be accomplished with several different drugs [1,11]. Surgery as a treatment option for TCC in the urinary bladder is used to obtain the tissue sample for histopathology, to attempt cancer removal from the bladder or to restore urine fl ow [12].…”

“…According to the World Health Organization (WHO) criteria for staging canine bladder tumors [9] 78% of dogs with TCC have been staged as T2 tumors (invading the bladder wall), while 20% were staged as T3 tumors (invading neighboring organs) [10]. TCC is commonly found in the trigonal location and in more than 50% of dogs involves the urethra which could lead to dysuria and partial or complete obstruction of the urinary tract [10,11]. An additional problem for dogs with TCC are the distant metastases seen in approximately 20% of cases at diagnosis and are associated with poor prognosis [2,11].…”

Lower Urinary Tract Cancer

“…Piroxicam is commonly favored as the first-line NSAID, although treatment with other NSAIDs such as deracoxib and firocoxib has also been reported. [23][24][25] Complete responses have been reported in a small number of cases treated with piroxicam alone, with an MST of 5.9 months. 24 The MST in a single report of 26 deracoxib-treated dogs was longer; however, those dogs received other chemotherapy agents after deracoxib.…”