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«CANINE BLADDER CANCER by Deborah W. Knapp, DVM, Dipl. ACVIM Cancer of the urinary tract in dogs can affect the kidneys, ureters, urinary bladder, ...»

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Results of another treatment study are expected to be published in the next 6 months that define another treatment option for dogs with TCC, that is “metronomic” chemotherapy. The term metronomic chemotherapy is used to describe the frequent (typically daily), low dose, oral administration of chemotherapy. In order to be given daily, the drug doses are quite low. In fact at the doses used, the chemotherapy is probably not having direct cytotoxic activity, i.e. not directly killing the cancer cells. This type of chemotherapy schedule was developed with the goal to block the formation of new blood vessels in the cancer, that is to have an “anti-angiogenic” effect. If the cancer cannot gain access to new blood vessels, it cannot grow. Recently, other mechanisms of cancer control have also been proposed for this metronomic treatment approach. The expected outcome of metronomic chemotherapy is that the cancer will stop growing for a period of time (ideally for many months or more). The cancer is not expected to shrink, but to stabilize in growth. Briefly, in a study at Purdue University, a series of 31 dogs with TCC were treated with low dose oral chlorambucil (also called leukeran). In the study, 1 dog had remission, and 20 dogs had stable disease, for a cancer control rate of 70%. This was encouraging since the cancer in all but 2 of the dogs had already developed resistance to other therapies. The median (“average”) length of life from the start of chlorambucil to death was 7 months, and this extended life was after other therapies had stopped working. The therapy was well tolerated with toxicity being very uncommon. The veterinarian can discuss with the pet owner whether “cancer control”, rather than cancer shrink is an appropriate goal for an individual dog.

Regardless of the treatment pursued, the typical plan followed in most dogs with TCC at Purdue University is to measure the extent of the tumor before treatment, and then to remeasure the tumor after 4-8 weeks of treatment (depending on the drug used). Various tests are also used to detect any side effects. If the tumor is shrinking or remaining stable in size after 4-8 weeks, and the dog is feeling well on that therapy, then the same treatment is continued. If the cancer is not responding, i.e. if it is growing, or if the dog does not feel well on that particular treatment, then a different treatment is initiated. After each 4weeks of treatment the tumor is remeasured to confirm the treatment is still being beneficial.

Beyond the options discussed above, there are other treatments that can also help dogs with TCC. One of the more active types of TCC treatment in humans is “platinum” chemotherapy, primarily consisting of the drugs cisplatin and carboplatin. These drugs have had considerable antitumor activity against canine TCC as well. Cisplatin, however, is not used in dogs very commonly anymore because of risk of damage to the kidneys. Carboplatin is used, but needs to be dosed carefully to limit the risk of side effects.

Carboplatin may have a new role when combined with a new type of drug – a demethylating agent. Stay tuned for results of ongoing research.

Pet owners that know humans with bladder cancer often ask why intravesical therapy is not done more often in dogs with TCC. Intravesical therapy, which refers to placing anticancer drugs directly into the bladder though a urinary catheter, is a mainstay in the treatment of humans with superficial TCC. The drug is expected to stay in the bladder where high concentrations can come in direct contact with the cancer. Initially, it was not known if intravesical therapy would be of benefit in dogs because TCC in dogs would be deeper in the bladder wall, and tumor masses would often be larger than those treated in humans. This would limit the access of the drug to the tumor. A clinical trial of intravesical therapy (specifically intravesical mitomycin C) in 12 dogs with TCC at Purdue University revealed two important findings. The first finding was that the antitumor effects were encouraging, consisting of partial remission in 5 dogs and stable disease in 7 dogs. Unfortunately, the second important finding was that in 2 dogs, the drug appeared to pass from the bladder into the blood stream and then throughout the body. These dogs had toxicity similar to what would occur with high dose intravenous chemotherapy. Although both dogs recovered, if a larger amount of drug were to be absorbed into the blood stream, it could cause more serious and life threatening side effects. For this reason, intravesical mitomycin C therapy is not typically given to dogs if there are other treatment options available.

In order to improve the outlook for dogs and human with invasive bladder cancer, the Purdue Comparative Oncology Program is conducting clinical trials in dogs with TCC. Dogs that take advantage of the clinical trials as well as standard care over the course of their cancer, can have longer survival, typically well beyond a year for many dogs. Clinical trials in dogs are similar to clinical trials in humans.

The dogs live at home with their families, and come into the Purdue University Veterinary Teaching Hospital periodically for evaluation and treatment. Quality of life for the dogs is the highest priority, so treatments evaluated in clinical trials are selected with the goal of having antitumor effects with low risk of serious side effects. The advantages for a dog participating in a clinical trial are that the dog is receiving treatment that is expected to be as effective or more effective than standard therapies, the dog is helping veterinarians learn important information that is expected to help other dogs and even humans with bladder cancer, and the dog is receiving some “hope” if standard therapy has failed. In some instances, participating in a treatment trial is less expensive than other treatments.

Many pet owners have observed humans undergoing chemotherapy and are concerned that some of the serious side effects of chemotherapy in humans will also be observed in pet dogs. Fortunately, most dogs treated with chemotherapy, experience much less toxicity than humans receiving chemotherapy. The side effects of chemotherapy are considered acceptable in most dogs. Treatment protocols are selected with the goal of maintaining or improving quality of life, at the same time the cancer is attacked. The pet owner should discuss the possible benefits and risk of specific medications that their dog may receive with the attending veterinarian. Cox inhibitors like piroxicam have few side effects. In some dogs (20%), however, piroxicam will irritate the stomach or intestine. Therefore, if a dog on piroxicam has loss of appetite, vomiting, or dark tarry-looking stools, it is safest to stop the piroxicam and consult the veterinarian before starting the medication again. The new cox inhibitors, selective cox-2 inhibitors, are not expected to cause stomach irritation as frequently as piroxicam does.

What is the prognosis for dogs with TCC? Early studies reported survival in dogs with TCC as "0 days". At that time, it was thought there was "no hope" and many dogs were euthanized at the time of diagnosis. It is not known how long dogs with TCC that are not treated will live. Survival is affected by the growth rate of the tumor, the exact location of the tumor within the bladder, and whether the tumor has spread to other organs or not. The median (“average”) survival in 55 dogs treated with surgery alone (before drugs that could help were identified) was 109 days. The median survival in dogs treated with early chemotherapy alone (cisplatin or carboplatin) at Purdue University was 130 days. Median survival with piroxicam treatment in 62 dogs with TCC was 195 days. As mentioned above, approximately 35% of dogs receiving mitoxantrone and piroxicam have remission, and the average survival is around 250-300 days. The survival times in all of these studies, however, varied tremendously from dog to dog. Some dogs died after only a few days, while others lived more than two years. As mentioned above, dogs who live the longest are those that receive more than one treatment protocol (one after the other switching therapies when the cancer begins to grow) during the course of the cancer. Factors that have been identified in our studies that negatively affect survival time include more extensive tumor within the bladder, spread of tumor beyond the bladder, and involvement of the tumor in the prostate gland.

Regarding metastasis of TCC in dogs, approximately 20% of dogs with TCC have detectable metastasis at diagnosis, and 50-60% have metastasis at death.

Although progress has been made, and TCC is considered a very “treatable” disease, there is still much to be learned. We are not satisfied with the “efficacy” of current therapy, especially long term. Therefore, we are continuing to study TCC to determine better ways to prevent, manage, and treat this cancer.

What symptomatic care can be given to dogs with TCC? Dogs with TCC are very prone to developing bacterial infection (cystitis) in the bladder. Therefore, frequent urinalysis, culture, and treatment with antibiotics may be necessary. A secondary bacterial infection can result in a sudden worsening in symptoms (blood in urine, straining to urinate) in dogs with TCC, and these dogs will improve with treatment with antibiotics. A frustrating aspect of urinary tract infections that is being encountered more often in recent years is the development of bacterial infections that are resistant to commonly used antibiotics. These infections often require treatment with injectable antibiotic therapy.

TCC can block the flow of urine into and out of the bladder. Complete obstruction can rapidly lead to a buildup of urea and life-threatening complications. If urine flow is obstructed, stents (small tubes) can be placed in the ureters or urethra, as needed, to open up the “channels” and restore urine flow. Our group is working closely with Dr. Larry Adams, a veterinary urologist at Purdue, to provide this opportunity for dogs that need it. Urethral stents are typically placed with fluoroscopic guidance in a non-surgical procedure. Ureteral stents can be placed surgically, and in some cases non-surgically. Another approach to bypass urethral obstruction is to place a cystotomy tube (small diameter tube that goes from the bladder through the wall of the abdomen to the outside) to allow emptying of the bladder.

Can TCC be prevented? Steps that can be taken to reduce the risk of TCC in dogs, especially in dogs in high-risk breeds (Scottish terriers, West Highland white terriers, Wire hair fox terriers, Shetland sheepdogs, beagles) include: (1) avoiding older generation flea control products, i.e. flea dips, (2) avoiding lawns treated with herbicides and pesticides, and (3) feeding vegetables at least three times per week. These will reduce the risk of TCC, although some dogs will still develop the cancer if these recommendations are followed. There are other causes for TCC that have not yet been identified. The role of exposure to cigarette smoke in bladder cancer risk in dogs requires more study, but it would be best to limit exposure to smoke as it can cause other disease in dogs too.

TCC screening for early detection. The Wellness Clinic in the Purdue University Veterinary Teaching Hospital is providing a TCC screening program for older dogs in high-risk breeds (Scottish terriers, West Highland white terriers, Wire hair fox terriers, Shetland sheepdogs, beagles). The screening includes an ultrasound exam of the bladder and tests performed on the urine at six-month intervals. This program is considered optional in the care of dogs. Although the screening is expected to lead to earlier diagnosis and the chance to treat the cancer before it becomes advanced, it is not yet known if it this screening program will improve the outlook for dogs or not. Pet owners who wish to schedule an appointment or check the availability and costs of the program can call the Purdue Small Animal Clinic at 765 494-1107.

Stay tuned, as an expanded option for TCC screening is under development in 2013.

What can be learned from dogs with TCC that will help human cancer patients?

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