Correlation of circulating plasma levels of cytokeratin 18 (CK18) with diarrhea in dogs with mast cell tumors treated with toceranib phosphate (Palladia)

Area of Study: 

Purpose of Study: 

Toceranib (Palladia) is in a new class of drugs currently being used with much success in the treatment of cutaneous mast cell tumors in dogs.  Toceranib is useful for treating other tumor types as well, even those tumors that do not respond to chemotherapy.  It is orally administered and  FDA-approved for use in dogs.  Unfortunately, a common side effect is diarrhea which impacts quality of life and requires stopping the drug, waiting a week or more, and restarting at a lower dose.  While quality of life is improved at the lower dose, toceranib may not be as effective at the lowered dose.

Cytokeratin 18 (CK18) is a protein expressed in cells that line the gastrointestinal tract. During cell death, CK18 is released into the bloodstream and thus can be measured.  Detection of CK18 can be used a marker for damage to the intestinal lining. 

The purpose of this pilot study is to determine if plasma CK18 levels can be used as a biomarker to help predict which dogs are at risk for having gastrointestinal side effects.

  1. Dogs with mast cell tumors that have been removed down to microscopic disease (i.e., postsurgery) are eligible to enroll in this study if they have no obvious evidence of tumor spread (metastasis).
  2. Pre-treatment screening will consist of bloodwork (CBC, chemistry panel, free catch urinalysis) prior to enrollment.

Dogs will not be eligible if they have serious kidney or liver disease, have been treated with chemotherapy or radiation therapy for their mast cell tumor, have concurrent blood cell changes (like severe anemia), or are currently treated with complementary or alternative medicines.  (A 5 day washout period before entry into the study will be sufficient for most medications

Client Responsibilities: 
  1. Dogs enrolled in the study will receive toceranib (Palladia) every other day by mouth.
  2. Dogs will come to the Veterinary Teaching Hospital for a total of 4 weekly visits (days 7, 21 and 28) for a physical examination and blood collection for plasma CK18 determination.
  3. Additional diagnostics (CBC, chemistry profile, urinalysis) will be performed at the start of the study (Day 0) and again at the end of the study on day 28.
Client Benefits: 

Although the study is completed in one month, all of the prescribed toceranib (Palladia) will be provided at no charge to the participating client for 4 months.  Toceranib can cost  $100 to $450/month depending on patient body weight.



Dr Chad Johannes: 515-294-4900

Dr Leslie Fox: 515-294-4900