Robyn Elmslie DVM, DACVIM (Oncology)
Melanoma is a malignant cancer arising from skin cells that make the pigment known as melanin. This cancer is relatively common in dogs over 10 years of age and is typically found in the mouth, toenail bed or on the skin. Melanoma is generally black in color due to the presence of the melanin pigment within the cancerous melanocytes, but on occasion some melanomas will be non-pigmented and difficult to distinguish from surrounding tissues. Unlike the case in humans, melanoma development in dogs is not caused by sun exposure. In fact, light coated dogs are rarely affected with melanoma, whereas melanoma is more common is dogs with abundant dark pigmentation on their skin or in their mouths such as Scotties, black Labradors, black Poodles and Chow Chows.
When melanoma develops in the mouth or in the nail bed, it typically has a very aggressive behavior, invading into the underlying bone and spreading quickly (metastasizing) to lymph nodes and lungs. Surgery is often very effective to eliminate the primary tumor but is not effective for the prevention of spread of the melanoma to the lungs and lymph nodes. Intravenous chemotherapy is minimally effective for prevention or treatment of melanoma metastasis in the lymph nodes, lungs or elsewhere. Thus alternative strategies for the prevention and treatment of advanced melanoma in dogs have been pursued.
In 2007, Merial released their melanoma vaccine (Oncept) for the prevention of spread of melanoma to the lungs and lymph nodes in dogs with stage 2 and stage 3 melanoma. The Merial melanoma vaccine for dogs consists of DNA encoding the gene for the human melanocyte protein tyrosinase. When administered to dogs, the vaccine triggers the dog’s immune system to mount an immune response against the human tyrosinase protein. Because the human tyrosinase protein is very similar to the dog tyrosinase protein, the immune response triggered by the vaccine cross-reacts with the dog tyrosinase protein expressed at high levels in the dog’s melanoma tumor cells. This is thought to trigger an immune response against the dog’s tumor. The immune response may also cause an attack against the dogs own skin cells (melanocytes), which may lead in very rare instances to some depigmentation. Some dogs may seem to have more gray fur after treatment with the vaccine as compared to prior to treatment.
Though several clinical trials have been performed, culminating in the USDA granting liscensure for the canine melanoma vaccine in 2010 , use of the vaccine remains controversial. The primary reason for the controversy is that none of the clinical studies performed to date have been done in a manner to truly test the efficacy of the vaccine. What has been missing thus far is properly performed randomized clinical trials, which are considered the gold standard studies to prove that a treatment or vaccine is effective. These studies are required by the FDA prior to approval of drugs or vaccines. However, the USDA (which approved the canine melanoma vaccine) has no requirement for such studies and thus the Merial vaccine was approved based on much less convincing trial data.
The aggressive nature of melanoma in dogs and short survival times after surgery emphasize the importance of developing an effective therapy for prevention of spread of this cancer. Ramos-Vera et al (Vet Pathol 2000) reported in a retrospective study of 388 dogs with melanoma in the mouth that the average survival time after surgery was only 173 days (<6 months). Published studies evaluating the survival times in dogs with melanoma in the mouth undergoing surgery and treatment with the Merial melanoma vaccine report average survival times of 599 days (20 months) or longer (Bergman et al Vaccine 2006; Grosenbaugh et al. AJVR 2011). These results, though not from randomized studies, are promising and have prompted many Veterinary Oncologists to recommend the vaccine for patients with stage 2 and 3 melanoma despite the lack of FDA-standard clinical trials. The vaccine is well tolerated and has not been reported to be associated with side effects requiring medical intervention. In patients with very large and aggressive melanoma, there may not be sufficient time for an immune response to be mounted against the tyrosinase protein to prevent progression of the melanoma. In fact, 15% of patients treated with the vaccine reportedly die within 3 months of initiation of treatment, presumably due to the aggressive nature of the melanoma and insufficient time for the vaccine to be effective.
At VRCC Oncology, our treatment recommendations for dogs with melanoma are tailored to the individual patient, and reviewed in a comprehensive manner with the pet owner. The melanoma vaccine is incorporated into the protocol when a high risk of spread of the melanoma is present.