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Tanovea® – A Novel Treatment for Lymphosarcoma

Lymphosarcoma is generally considered the most treatable cancer in veterinary medicine. We have multiple treatment options for this cancer, ranging from prednisone alone to aggressive multi-drug chemotherapy protocols. The most commonly used protocol is a CHOP protocol, and this protocol uses vincristine, cyclophosphamide, Adriamycin®, and prednisone. Approximately, 80 – 90% of dogs will go into remission on this protocol, and the average first remission is typically 6 – 10 months. If dogs survive the first year, 25% will live over 2 years.

There are multiple variations on the multi-drug theme, and they usually are given an acronym based on the drugs in the protocol. So, you will see names like COP, CHOP, COAP, PACO, MOPP, DMAC, and the list goes on and on. In reality, in spite of all of these different protocols, we have made glacial strides in improving survival over the past 20 years. That’s where Tanovea comes in!

Tanovea®-CA1 is the brand name for rabacfosadine, which was also known as GS-9219 or VDC-1101. This is double prodrug of the guanine nucleotide 9-(2-phosphonylmethoxyethyl) guanine (PMEG). Now that’s a mouthful! Basically, Tanovea® preferentially targets activated or cancerous lymphoid cells. Once inside the cells, Tanovea® undergoes enzymatic changes to become PMEGpp, and this compound inhibits DNA synthesis and repair. If the lymphoma cells can’t proliferate or repair damage, they die. Hence, Tanovea® is a lymphoma drug.

What Tanovea does

Now, here are oncology statistics for you. The overall response rate is the number of dogs that respond to the drug, and in the initial studies, Tanovea® demonstrated a response rate of almost 80%. Of the dogs that responded, the remission rate was about 130 days.

Response rate on Tanovea

Tanovea® has also been evaluated in dogs with relapses of their lymphoma after being treated with a chemotherapy protocol that included Adriamycin®. Of these dogs, 74% responded to Tanovea®, and the remission rate was 108 days. As expected, this study found that dogs with B-cell lymphomas had longer remissions than dogs with T-cell lymphomas.

Tanovea® has been evaluated in combination with Adriamycin®. Because Adriamycin®-based protocols, such as CHOP, generally require 12 – 16 visits for treatment, this protocol has been evaluated to decrease the total number of treatments to 6. The response rate was 84%, which was a little lower than CHOP alone, and the average remission was 194 days.

All of this sounds great, right? Well, lets talk a few minutes about the side effects of Tanovea® because it has some side effects that are very different than other chemotherapy drugs. The most common side effects are gastrointestinal with a decreased appetite being seen most frequently. Diarrhea is the second most common GI side effect followed by vomiting. Weight loss and lethargy are also reported. Most of the affected dogs have mild, self-limiting side effects.

Tanovea® can affect blood cells, and a low white blood cell count is the most frequent hematologic abnormality. Low platelet counts can be seen, too. Liver enzymes can increase, although this usually resolves without specific therapy.

Now, lets talk about the more unusual side effects. Tanovea® causes some dermatologic abnormalities. Some dogs will develop redness of the skin, loss of hair on their ears, and ear infections. Generally, we need to address their skin problems at this stage, or the dogs can develop crusty/ulcerative lesions that are quite painful. Some dogs will develop an intense itch. To help with these skin lesions, topical anti-inflammatory medications are often required, and some dogs need systemic antibiotics or prednisone in addition to decreased drug doses with increased time between treatments.

Crusting, ulceration and hyperpigmentation

The most severe side effect associated with Tanovea® is pulmonary fibrosis. This is basically a thickening of the lungs. It is reported in approximately 4% of dogs treated with Tanovea®, but it can be fatal. It usually develops after the dogs have completed therapy, but we will usually monitor thoracic radiographs at 2 – 3 months during treatment to ensure that the lungs still look normal. When the dogs develop this problem, they will start exhibiting difficulty breathing, exercise intolerance, or coughing. Steroids can help stabilize or improve dogs that develop this problem.

Comparison of normal lungs vs. lungs with pulmonary fibrosis

Because of these respiratory effects, dogs with pre-existing disease of the lungs should not be given Tanovea®, and West Highland white terriers should not be given the drug, as they are the breed most frequently affected with pulmonary fibrosis.

When you read the label on this drug, the manufacturer recommends that chemotherapy-resistant gloves be worn when handling feces, urine, vomit, or saliva for 5 days after treatment. Waste material should be placed in a plastic bag and sealed. Tanovea® can cause birth defects in people, and it can affect fertility in men and women. Kind of scary, huh? Mostly, this is common sense and not a reason to be terrified to treat your dog.

ulceration of the skin

The last thing to mention is cost. Unfortunately, the drug cost is significantly higher than some of the generic chemotherapy drugs that are used in our standard chemotherapy protocols. However, Tanovea® is labeled for 5 doses when used as a single agent treatment, and when combined with Adriamycin®, the dogs are given 3 doses of each drug.

To wrap this up, Tanovea® is a novel drug with a very unique mechanism of action, and, based upon the clinical trials that have been performed, it works! Tanovea® is being used most frequently as a first-line rescue agent at this time, but there are certainly instances when it may be considered as the first-choice chemotherapy drug. Tanovea® has some unique side effects, and careful monitoring is required to prevent life-threatening side effects.

Happy Dog

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