The Dog Cancer Survival Guide (120 page)

Like oral melanomas, digit melanomas require an aggressive surgery to control the local disease. The best-case scenario is usually toe amputation, which can be done if there is no detectable local or distant metastasis and wide margins (greater than two centimeters) can be obtained in the surgery. If these wide margins are not possible, leg amputation is considered. Median survival times of twelve months are typical with these surgeries.

If the owners decline limb amputation and the surgeon can’t get two centimeter wide margins with a toe amputation, radiation therapy should be used to try to clean up the dirty margins (kill the remaining microscopic cancer cells). Radiation should also be given to any regional lymph nodes that test positive for metastasis.

Dogs with digit melanoma usually die due to distant metastasis, especially those with larger tumors or metastasis at the time of diagnosis. To combat or delay metastasis, which occurs in 30-60% of dogs with digit melanoma, the melanoma vaccine should be used following surgery and/or radiation. As with oral melanoma, chemotherapy, specifically carboplatin, may be considered. Also as with oral melanoma, the melanoma vaccine is more routinely recommended instead of chemotherapy (see below). In a recent study, dogs treated with both locoregional control (surgery and/or radiation) and the melanoma vaccine had a median survival time of about sixteen months, with 63% still alive after one year. In the same study, metastasis at the time of diagnosis reduced median survival times – dogs with metastasis had a median survival time of three and a half months, while treated dogs without metastasis had a median survival time of almost eighteen months.

Chemotherapy used as a standalone treatment for a primary digital melanoma is not recommended, as it is not effective enough.

While benign skin melanomas are not malignant in general, some can have malignant potential and characteristics. For this reason, they should be treated. Surgery is the first therapy given to dogs with benign skin melanomas, affording them a median survival time of twenty-four months. Some dogs can be cured with this surgery alone.

Malignant skin melanomas must be treated with aggressive surgeries, with wide (greater than 2 cm) margins. These surgeries generally result in median survival times of seven to eleven months. If wide margins cannot be or are not obtained, a scar revision (second surgery) can be done. If that’s not feasible, radiation therapy may be used to delay recurrence at the surgery site.

Systemic therapy is also recommended for malignant skin melanomas (melanoma vaccine, or the chemotherapy drug carboplatin, see digital melanoma section above), although we do not yet know whether survival times are lengthened with this therapy.

A new and exciting treatment option for all melanoma types is immunotherapy; a new vaccine is available that can be used to stimulate the immune system to fight the cancer cells. It can be used with all stages of melanoma, although it is less effective for stage IV melanoma with distant metastasis, or for dogs with measurable local disease (a tumor which has spread and can be seen and measured).

Traditionally, vaccines are used to prevent infections; this vaccine is very different. The canine melanoma vaccine (which is USDA-approved for dog melanoma) is a therapeutic vaccine, used not to prevent, but to treat the illness. I am excited about this vaccine, not only because it helps dogs with melanoma, but also because I was involved in the clinical trials. Here’s how the vaccine works.

There is a normal body protein called tyrosinase, present on the outside of some cells in the body. Melanoma cells happen to manufacture a great deal of this protein. Because the immune system does not normally attack its own cells, the immune system does not recognize or attack either melanoma cells or regular cells when they have tyrosinase present.

This vaccine cleverly uses tyrosinase, created from another animal’s DNA (humans, actually), to stimulate the immune system to target cells with a lot of this protein. The human version of tyrosinase is just different enough from dog tyrosinase to raise an alert in the immune system. The system mobilizes to destroy the new tyrosinase and anything similar to it. Melanoma cells are targeted because of their large amounts of tyrosinase, while normal cells, which have much less, are largely unaffected.

My mentor, Dr. Philip Bergman, led the studies of the DNA melanoma vaccines that led to the development of this vaccine, and I participated in the ongoing trials during my residency at Animal Medical Center (AMC) in New York City. The hospital partnered with Memorial Sloan-Kettering Cancer Center, also in New York City, to test a human melanoma vaccine. The studies produced significant and exciting results.

(Dogs and humans are similar physiologically, so dogs are often involved in human cancer research.)

Early studies involving dogs with advanced melanoma (stage II, III and IV) showed a median survival time of thirteen months for dogs on the trial vaccine, compared to five months for dogs on standard therapies. Importantly, the vaccine was demonstrated to be safe and active.

Further studies involved about 350 dogs at AMC. In these trials, dogs with minimal residual disease (MRD) remaining after local control (surgery and/or radiation), that were also treated with the vaccine, had increased survival time, over thirty-three months, versus dogs without the local control, who experienced eighteen months. To maximize the vaccine’s effectiveness, we must achieve minimal residual disease: the primary tumor must be completely resected and/or treated with radiation (for incomplete margins). Non-resectable tumors should be treated with radiation therapy. The vaccine is also more effective when local lymph nodes are either negative for metastasis or, if positive, are surgically removed or treated with radiation. This does not apply to stage IV dogs with distant metastasis.

It can take months to develop significant immune response, so I advise starting to use the vaccine as soon as possible. There is some evidence that starting the vaccine before radiation treatments is helpful. This is because tumor cells release tyrosinase as they are killed by radiation, which can enhance the immune system’s response.

The vaccine is administered through a transdermal device that goes into the muscle of the inner thigh. There is no needle involved, which allows the device to distribute the vaccine evenly into the muscles. The initial treatment consists of four doses of vaccine given at two-week intervals. After that, booster doses are administered every six months. Some dogs develop a low-grade fever, which doesn’t last long. Mild skin reactions were noted in 5% of dogs in the studies, usually some skin redness that resolved quickly without the need for treatment. In some rare cases, dogs lost some pigment in their coats – in other words, some of their black coat turned white. There has been very little evidence of toxicity due to the vaccine.

In 2007, the USDA gave a conditional license to the vaccine, which allows a new treatment to be used, while still being monitored for safety and efficacy. In January of 2010, a full license was issued to Merial, the manufacturer, and Merial started selling Oncept, the commercial version of the vaccine. This is the first and only vaccine approved for the treatment of cancer, in any species, and is available only through medical oncologists.

As an interesting side note, human clinical trials are being conducted at Memorial Sloan-Kettering for a melanoma vaccine very similar to the canine version. I highly recommend using this vaccine, in conjunction with surgery and radiation; consult with an oncologist to determine whether it is appropriate for your dog’s case.

Also, please note that while it may be tempting to think this vaccine can be used to prevent melanoma, this is not the case. It has only been tested in dogs with a diagnosis of melanoma, and the overall incidence of canine melanoma is too low to justify giving this vaccine to all dogs to attempt to prevent the disease.

While melanoma can be a distressing disease, there are many options for treatment. Treated dogs live longer and enjoy a good quality of life.

“Love your dog and give her the best you have, understand that this is an important and difficult time for both of you. Find a network of people who have been through it to support you, and get as much info as you can beyond what your own vet is telling you.”

- Ellen Slater, Redmond, Oregon

C
hemotherapy is an emotionally charged word for many people, because it has a reputation for terrible side effects, when used in human cancer. As we’ve pointed out before, using chemotherapy drugs to treat dogs is a different situation. It’s true that most chemotherapy drugs have some side effects for dogs, though they are usually manageable and worth the effect of the drug. Unlike people, most dogs do not become seriously ill on chemotherapy, because we do not use high, curative doses. Most dog owners who choose chemotherapy are happy with the results and pleasantly surprised that their worst fears didn’t come true. Oncologists are experts at managing side effects, and newer treatments often minimize side effects even more.

As Dr. Dressler pointed out in
Chapter 1
, our brains can create “rules of thumb” about stressful or painful events. If you’re finding yourself breathing a little harder, or resistant to finding out more about the chemotherapy drugs that are recommended for your dog’s cancer treatments, try his Three Deep Breaths exercise. If you’ve got a rule of thumb about chemotherapy, this chapter will likely trigger it.

Alkylating Agents target DNA in several ways: they cross-link, or bind, strands of DNA together; create breaks in the DNA that cannot be repaired and alter the actual function of DNA. As a result, the cell cannot divide, and dies. These agents are most active in the resting phase of the cell cycle.