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Issue: 70 - Oct 15, 2014
Mastocytoma: Comparing Options of Traditional Therapy to Kinavet-CA1® (masitinib mesylate)
By: AB Science
AB Science

Background: Mast cell tumors (MCTs) are among the most common forms of cancer in dogs [1]. The origin of MCTs is a deregulated proliferation of normal cells in the skin (mast cells) that leads to a dangerously abnormal growth of these cells and formation of a tumor. MCTs have various forms and vary widely in size, shape, appearance, texture, and location.  Some breeds, such as boxers and pugs, tend to display higher predisposition to developing MCTs in their lifetime [2]. These tumors often behave in an aggressive manner, metastasizing to secondary body locations and releasing chemicals that cause systemic problems such as loss of appetite, vomiting, diarrhea, abdominal pain, itchiness, lethargy, and anemia. While there are many factors that contribute to tumorigenesis, the c-KIT proto-oncogene has been implicated in MCT growth and proliferation [3].  Mutations in c-KIT, a protein expressed by mast cells, are strongly associated with poor prognoses [4].

Diagnosis: Diagnosis of a mast cell tumor is usually made using a needle aspiration biopsy of the tumor, which will typically show a large number of mast cells for a positive diagnosis, although poorly differentiated mast cells may have few granules and be more difficult to identify. A surgical biopsy is required to find the tumor's Patnaik system grade [5].  More recently a high and low grade system of evaluation has been implemented.

  • Grade I - well differentiated, mature cells with low potential for metastasis
  • Grade II - intermediately differentiated cells with potential for local invasion and moderate metastatic behavior
  • Grade III - undifferentiated, immature cells with a high potential for metastasis

The disease is also staged via x-rays, ultrasound, or lymph node, bone marrow, or organ biopsies:

  • Stage I - a single skin tumor with no spread to lymph nodes
  • Stage II - a single skin tumor with spread to lymph nodes in the surrounding area
  • Stage III - multiple skin tumors or a large tumor invading deep to the skin with or without lymph node involvement
  • Stage IV - a tumor with metastasis to the spleen, liver, bone marrow, or with the presence of mast cells in the blood

Outlook after Diagnosis: Surgical excision is the treatment of choice when possible. Antihistamines may be given prior to surgery to protect against the effects of histamine released from the tumor. Because of the tendency for the tumor cells to proliferate beyond the margins of the tumor, wide margins are required for a successful tumor resection.  Depending on the grade, surgical margins may be up to approximately 1 inch from the tumor.  

Patients with Grade I or II MCTs capable of being completely removed tend to have a good prognosis after excision, often without additional treatment. Tumors that have spread to the lymph nodes or other parts of the body tend have a poor prognosis—unfortunately, any dog with a Grade III tumor will likely have a poor prognosis.

For nonresectable, incompletely resected, or recurrent tumors, the traditional treatments have included radiation therapy, chemotherapy, corticosteroids, or a combination thereof.  Radiation therapy and chemotherapy are both cytotoxic and indiscriminately kill both tumor cells and living, healthy cells. 

Chemotherapy is often associated with both acute and chronic toxicity.  Lomustine, a common chemotherapeutic agent, has been associated with delayed, chronic hepatic toxicity that could be irreversible and fatal [6]. 

Radiation therapy is a cost-intensive option that is available and typically requires a referral to a specialty center.

Corticosteroids are a common first-line medical treatment for MCTs. Prednisone, for example, has been shown to be effective in treating canine MCTs by reducing inflammation, though it has limited efficacy as a single agent [7].  It is frequently used in combination therapies with other therapeutic agents.

New Treatment Option for Canine MCT: A novel class of drugs called tyrosine kinase inhibitors—drugs that target specific receptors with unprecedented precision—represent a new chapter in the development of anti-cancer treatment modalities.  Kinavet-CA1 is rapidly gaining awareness as a result of its safety and efficacy.  Veterinarians have been discovering the ease with which they can incorporate this first-line treatment into their current MCT therapy protocols.

In Practice: A report from Silicon Valley Pet Clinic in Santa Clara, CA documented the clinical progression of a 10 year old Rottweiler mix named Oz during Kinavet-CA1 therapy for a grade II MCT.

Kinavet-CA1 targets mast cells by inhibiting a class of receptor proteins called tyrosine kinases, which include the protein c-KIT.  Inhibition of c-KIT can cause apoptosis (programmed cell death) of the mast cells.  As a result of its targeted mode of action compared to cytotoxic chemotherapy, Kinavet-CA1 has demonstrated an appealing blend of efficacy and safety while helping to prevent future occurrence.  As a once-daily oral tablet, Kinavet’s ease of administration helps to boost therapeutic compliance. 

Clinical Results: Oz’s grade II mast cell tumor had metastasized to the local regional lymph nodes by the time it was diagnosed in September 2012.  By December 2012, he had developed multiple cutaneous MCTs throughout his body.

Oz began Kinavet-CA1 therapy on January 19, 2013.  By the end of the week, Oz displayed noticeably fewer open lesions and many smaller lesions had disappeared entirely. 

By February 2, 2013 the majority of small lesions had disappeared and the bi-weekly CBC panel continued to verify that Oz was experiencing no adverse effects.  By February 16, 2013 the final remaining lesion on his side had disappeared, save a few scabs.

In Oz’s case, Kinavet-CA1 progressively reduced the multiple mast cell tumors in size and ultimately obliterated them within five weeks. Despite his owner’s demanding work schedule, she was able to consistently treat him once daily for the course of the treatment.

Oz, with multiple MCTs prior to treatment with Kinavet-CA1   1/19/2013

Oz, five weeks post treatment with Kinavet-CA1 2/22/2013      

Looking Ahead: Currently AB Science is conducting a phase 3 canine MCT study in the United States and Europe. Veterinarians who are interested in participating in this study are encouraged to contact AB Science at (908) 273-8700 for more information on this exciting clinical trial. 

Oz’s success with Kinavet-CA1 is representative of patients that demonstrate a good clinical response to this TKI.  If you are considering treating a patient for MCT, please visit as a resource for additional information and scientific data and to learn about our development program. Your AB Science representative is always available to answer any technical inquiries and provide credible references. To order Kinavet-CA1 for your practice, please contact your Henry Schein Animal Health sales representative.


1. Brière C. (2002). Use of a reverse saphenous skin flap for the excision of a grade II mast cell tumor on the hind limb of a dog. Can Vet J 43(8): 620–2. PMC 339404; PMID 12170840.

2. McNiel, E. A., Prink, A. L., & O'Brien, T. D. (2006). Evaluation of risk and clinical outcome of mast cell tumours in pug dogs. Veterinary and Comparative Oncology4(1), 2-8.

4. Webster, J. D., Yuzbasiyan-Gurkan, V., Kaneene, J. B., Miller, R., Resau, J. H., & Kiupel, M. (2006). The role of c-KIT in tumorigenesis: evaluation in canine cutaneous mast cell tumors. Neoplasia (New York, NY)8(2), 104.

5. Webster, J. D., Yuzbasiyan-Gurkan, V., Miller, R. A., Kaneene, J. B., & Kiupel, M. (2007). Cellular proliferation in canine cutaneous mast cell tumors: associations with c-KIT and its role in prognostication. Veterinary Pathology Online44(3), 298-308.

6. Vandis, Maria; Knoll, Joyce S. (2007). Cytological examination of a cutaneous mast cell tumor in a boxer. Veterinary Medicine (Advanstar Communications) 102(3): 165–168.

6. Kristal, O., Rassnick, K. M., Gliatto, J. M., Northrup, N. C., Chretin, J. D., Morrison-Collister, K., ... & Moore, A. S. (2004). Hepatotoxicity associated with CCNU (Lomustine) chemotherapy in dogs. Journal of Veterinary Internal Medicine18(1), 75-80.

7. McCaw, D. L., Miller, M. A., Ogilvie, G. K., Withrow, S. J., Brewer, W. G., Klein, M. K., ... & Anderson, S. K. (1994). Response of canine mast cell tumors to treatment with oral prednisone. Journal of Veterinary Internal Medicine8(6), 406-408.