Canine Mast Cell Tumor
Mast cell tumors are common skin tumors in dogs. They account for 20-25% of all skin tumors in dogs. They are a cancer of mast cells, which are cells important in regulating inflammation and immune responses. The tumors may occur in dogs that have a history of allergic skin disease. About 50% occur along the trunk and perineum, 40% along the extremities and 10% along the head and neck. They can occur as a solitary lesion or be multiple. They can be haired, ulcerated, pedunculated, etc., and because of their different appearances are often called the “great imitator”. In most cases, dogs have a history of the mass being present and changing in size over time.
With mast cell tumors, several factors have been shown to be prognostic:
1. Grade: Low-grade tumors (Grade I) do better than high grade (Grade III).
- Clinical stage: Tumors spread throughout the body carry a worse prognosis.
- Location: Tumors along the perineum, gums, and oral cavity carry a worse prognosis.
4. Systemic signs: Animals that are sick due to systemic disease often do worse.
5. Completeness of surgery to remove the tumor: complete removal better. - Mitotic index: greater than 5 carries correlated to survival times of 2 months.
Various grading schemes exist for grading mast cell tumors, with the most commonly accepted scale being a 3-tiered scheme. Our recommendation for most cases is as follows with respect to the grade:
If grade I or II and the surgery was complete (all cancer removed) then the dogs are simply followed over time. With a complete surgery, up to 90-100% may never recur again. If surgery is incomplete we recommend a second surgery. If this is not possible due to location then we recommend radiation therapy (mast cell tumors are very responsive to radiation therapy and local control of 90% has been noted) for the tumor. If radiation therapy is declined, chemotherapy could be considered to prevent tumor recurrence, although it is not a direct substitute for adequate surgical control and/or radiation therapy. More recent studies have shown that there is a subset of grade II tumors that behave more aggressively. It is recommended that all grade II tumors are evaluated with special stains (proliferation markers and genetic analysis) to tease these out. If a high-grade II tumor is identified, then these dogs are treated with chemotherapy.
If a grade III tumor is found and completely removed, we still recommend follow up chemotherapy because of the aggressive nature of this tumor and high potential for metastasis. With surgery alone, the median survival (50% alive) is 6 months. With surgery followed by chemotherapy, the median survival increases to 12 months. In case of incompletely excised grade III tumors, we recommend either a second surgery or radiation therapy. One study found that dogs with incompletely excised grade III mast cell tumors followed by radiation therapy had a median survival of 20 months. It is our belief that with chemotherapy, these dogs would likely do even better. However, large tumors (>2 inches) and tumors with high-grade features may still only carry average survival times of 6 months depending on other prognostic factors. Typically combining surgery with radiation therapy and chemotherapy improves the prognosis.
In cases where the tumor cannot be removed due to size or location we typically offer palliative radiation therapy and chemotherapy. This particular protocol involved 4 weekly doses of radiation followed by a 15-week course of chemotherapy and is intended for patients that cannot be cured as it offers improvement in clinical signs and reduction in the size of the tumor. A recent study evaluated 65 dogs treated in this manner and found that 42% of the tumors responded (completely or partially reduced in size) and an additional 30% had stabilization of their disease. Nearly half of these dogs had cancer spread and were treated after failing other traditional therapies which explains the relatively short duration of response (2 months) and overall survival time (3 months). Factors that significantly affected outcome were: grade of the tumor (grade III did worse), location of the tumor (mucosal tumors experienced remission duration of 5 months and an overall survival of 7 months), and if chemotherapy was continued after radiation therapy (survival of 3.5 months vs 3 weeks if it was not). Although the survival time reported in this study is poor, palliative radiation therapy and chemotherapy can be offered for cases in which there is no other treatment option.
Palladia is a new drug and has become the first canine anti-cancer therapy approved by the FDA in the United States to treat mast cell tumors. The generic name is Toceranib Phosphate and this agent is the first of its class in veterinary medicine. Unlike traditional chemotherapy, Palladia is a more “targeted” chemotherapy agent. The target molecules for this particular drug are VEGFR, PDGFR, and c-kit, all proteins involved in cell growth and survival. Specifically, Palladia is labeled for use in mast cell tumors, which over-express c-kit in up to 50% of tumors.
In a clinical trial of dogs with mast cell tumors, Palladia helped nearly 70% of dogs to destroy, reduce, or halt the growth of tumors. In certain mast cell tumors, Palladia can “turn off” the abnormal protein signal (c-kit) that often plays a role in their growth and development. Interestingly, the drug has also been shown to reduce/slow the growth of other types of cancer by decreasing a tumors blood supply (by inhibiting both VEGFR and PDGFR) and limiting its nutrients.
Palladia is an oral anticancer medication given on an every other day basis at home. Although Palladia is oral and “targeted” in nature, severe side effects can occur if early signs are not detected. The most significant side effects may be GI in nature and include vomiting, nausea, diarrhea, loss of appetite, and weight loss. Additional side effects include neutropenia, anemia, and muscle cramping. If caught early and treated aggressively, most side effects are reversible depending on the patient’s clinical status.