NEVOG News
New developments in the treatment of canine transitional cell carcinoma (TCC) of the urinary bladder - New use for an old drug
By Andy Abbo DVM, MS, DACVIM - Oncology, New England Veterinary Oncology Group
Transitional cell carcinoma (TCC) of the urinary bladder is the most common cancer of the canine urogenital tract and is challenging disease to manage that arises from malignant transformation of epithelial cells lining the urinary bladder, urethra, prostatic ducts and renal pelvis.
Treatment of TCC is directed at both local and distant control of disease with most dogs succumbing to failure of local disease control resulting in urinary tract obstruction. Treatments evaluated to date have limited response rates and efficacy in controlling both local and distant disease.
Surgery is generally not considered feasible due to most tumors being either diffusely affecting the urinary bladder at diagnosis or trigonal location; however, tumors located in the apex may be surgically excised. These excisions can be performed if there is no evidence of distant metastasis, though relapse is often noted within a 3-to-6-month period without adjunct therapy.
Relapse may occur due to the "field effect," which states that carcinomas (often of transitional cell origin) develop within a contiguous field of pre-neoplastic cells. These cells already possess genetic alterations associated with the process of carcinogenesis, which leads to a sub-clone of cells that ultimately develop into invasive carcinoma. The role of radiation therapy in the management of TCC is not well defined at this time.
Medical management with COX inhibitors and IV chemotherapy has been the mainstay of therapy with response rates reported of 18-38 % and survival times ranging from 6-12 months. However, some of the longest surviving dogs, in my opinion, receive multiple different chemotherapy protocols and surgery is combined ONLY if localized disease is noted in a location that allows for safe resection (i.e. apical or mid body location). COX inhibitors such as Piroxicam, Carprofen and Deramaxx have been evaluated, have anticancer effects and are well tolerated. Other NSAIDs are expected to yield similar responses but have not been fully evaluated in the veterinary literature.
In a recently published prospective clinical trial to evaluate the efficacy of single agent vinblastine for the treatment of canine TCC1, researchers at the Purdue Comparative Oncology Program found that vinblastine has antitumor activity against TCC both in vivo and in vitro.
Vinblastine has efficacy when used either as a single agent or in combination protocols when used to treat humans with the muscle invasive form of TCC which is similar in biological behavior to the naturally occurring disease in canines. In laboratory studies, vinblastine was shown to have potent anti-proliferative effects against canine TCC cells in vivo2 and vinblastine concentrations that inhibited cell proliferation by 50% in canine TCC cell lines were lower than serum concentrations reported with standard in vitro dosing further supporting the use of vinblastine in the treatment of canine TCC.
Twenty-eight privately owned client dogs were enrolled in this trial and tumor responses were noted in 10 dogs (36% partial remission, 14% progressive disease). No complete responses were noted. The median survival time was 147 days (range, 28-476 days) from first vinblastine treatment to death and 299 days (range, 43-921 days) from diagnosis to death with a median progression free interval of 122 days (28-399 days).
This new data supports that vinblastine as a single agent is a viable option for pet dogs with clinical responses noted and limited toxicity. Vinblastine also has the advantage of being associated with less expense to clients than other historical agents. Interestingly many of the dogs enrolled in this study had failed previous therapy with other agents supporting its use as both a primary and rescue agent. Further studies will need to be performed to evaluate the combination of vinblastine with COX inhibitors and other chemotherapy agents.
1 E.J. Arnold et al., J Vet Intern Med 2011;25:1385-1390
2 Knapp/ Paolina- unpublished data

Dr. Andy H. Abbo, Diplomate ACVIM (Oncology)
"Oncology is special to me because with continued clinical research and current therapies, we can not only provide for excellent quality of life, but now, can also provide the best therapies for pets and their people."
A graduate of Kansas State University College of Veterinary Medicine, Dr. Abbo furthered his education by receiving a Master of Science in Veterinary Clinical Sciences at Purdue University School of Veterinary Medicine. One of his honors and awards, as a Resident at Purdue, includes "First Place - Phi Zeta Osborne Clinical Investigator Research." He is a member of ACVIM, MVMA and VCS.
NEVOG is pleased to announce that we are currently available to see appointments at our Cape Cod satellite office located within Cape Cod Veterinary Specialists in Bourne, MA. We are available on Tuesday and Thursday of each week for routine chemotherapy appointments as well as new consultations. If you have any questions or feel we can be of service to your clients please do not hesitate to call for consultation or referral.
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