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S. Ettinger1
Dr Sue Cancer Vet PLLC and Animal Specialty & Emergency Center Wappinger Falls, NY, USA
MCT are the most common cutaneous tumor in dogs, accounting for 16 to 21% of skin tumors. While many MCT are often treatable with surgery alone, in some cases surgery may be declined, not an option based on size, or there is advanced (metastatic) disease. Palliative and supportive care is important in these cases.
Dogs with low grade/grade 1 or grade 2 that have low proliferation scores and are c-kit negative can typically be managed with local therapy (surgery +/- radiation). Chemotherapy should be considered for: high grade/ grade 3, dogs with distant metastasis, lymph node metastasis, C-kit mutation positive dogs, dogs with high MCT proliferation scores, and for non resectable MCT in the neo-adjuvant setting. Dogs with multiple MCT in a short time period may also be considered for chemotherapy.
Disease symptoms can be complicated by signs attributable to release of histamine, heparin and other vasoactive amines from the MCT. Darier’s sign refers to the wheal & flare in surrounding tissues following manipulation of the MCT and is caused by mast
cell degranulation. GI ulceration is due to histamine stimulation of H2 receptors on parietal cells that increased HCl. GI ulceration causes vomiting possibly with blood, melena, anorexia, and abdominal pain. GI ulceration is noted in 35 to 83% necropsy specimens.
Surgery: Surgery is the ideal treatment in areas amenable to wide resection. The recommendations for margins have historically 3 cm, but 2 cm lateral margins may be adequate for most (Simpson 2004). For small and lower grade, extensive deep margins are just as crucial: 1 fascial plane deep, 4 mm deep margins. The majority of naïve dermal MCT are intermediate or low grade will be cured with surgery alone, provided site is amenable.
In some locations, wide margins are often not possible, such as the distal limb. In my opinion, amputation is probably too aggressive. But further therapy will likely
be needed after surgery. Post-operative options include external beam RT, scar revision, and chemotherapy. Some tumors are also too large to remove
Radiation therapy (RT) is recommended when wide surgical excision not feasible. Monotherapy has varying control rates with 1 year control rates of 50%. This
is in contrast to surgery to achieve clinical stage 0 (microscopic disease) followed by full course RT, (typically 15 treatments over 3 weeks) which has high control rates of 85-95% 2-year control rates for grade 1 and 2.
For macroscopic MCT, the combo of steroids with palliative radiation have been reported to have an improved overall response rate (ORR) of 75%. Palliative radiation is typically weekly radiation for 4 weeks.
Steroids As a single agent in grade 2-3 MCT, overall response rate (ORR) was 20% (5 of 25). (McCaw 1994). But prior to RT for non-resectable grade 1-3, RR was higher at 75% (18/24). (Dobson 2004) When given prior to surgery (neoadjuvant) for grade 1-3 pre-op ORR was 70%. (Stanclift, 2008),
Chemotherapy: Chemotherapy can be considered palliative for non-resectable MCT. Single agent chemotherapy has variable response rates, but studies have shown that combination therapies offer improved efficacy. I prefer the combo of vinblastine and prednisone, which has reported efficacy for gross disease of 47%.
Palladia (toceranib phosphate) is an oral Tyrosine kinase inhibitors (TKI) that blocks activity of multiple receptors and selectively targets split kinase family of RTKs. It exerts antiangiogenic and antiproliferative effects. The oral bioavailability is 77%. Palladia is labeled for dogs with grade 2 or 3, recurrent cutaneous MCT, + regional LN involvement, and was FDA approved in June 2009. Palladia is 1st anti-cancer drug FDA approved for dogs.
In the clinical field study of single agent Palladia (London 2009), this was a multi-center placebo-controlled, double-blinded study looking at the objective response (PR or CR) to single-agent Palladia @ 3.25mg/kg EOD. The biologic response rate was 59.5% for all dogs (blinded + open): CR 16%, PR 31.3%, and SD 12.2%. The odds ratio of OR was 6.5x higher in Palladia- treated patients vs. placebo. Grade 2 MCT had better outcomes than grade 3, and had a significantly longer time to progression (TTP) and significantly longer response duration. Palladia was effective with or without c-Kit mutation (positive: 69% response; negative: 37% response)
Adverse Events (AE): GI side effects were most common AES, >10% Palladia dogs (during blinded phase). Neutropenia was the most common lab abnormality.
An Urban Experience

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