Palladia Treatment

Palladia (toceranib phosphate) tablets

Client Information Sheet

This summary contains important information about Palladia. You should read this information before you start giving your dog Palladia and review it each time the prescription is refilled as there may be new information. This sheet is provided only as a summary and does not take the place of instructions from your veterinarian. Talk with your veterinarian if you do not understand any of this information or if you want to know more about Palladia.

What is Palladia?
Palladia, a tyrosine kinase inhibitor, is a drug used to treat mast cell tumors, a common
form of cancer that affects dogs.

Palladia works in two ways:
    • By killing tumor cells.
    • By cutting off the blood supply to the tumor.

Your veterinarian has decided to include Palladia as a part of your dog’s treatment plan
for mast cell tumor. Other types of treatment, such as surgery, drug treatment and/or
radiation may be included in the plan. Be sure to speak with your veterinarian about all
parts of your dog’s treatment plan.

What do I need to tell my veterinarian about my dog before administering Palladia?
Tell your veterinarian about all other medications your pet is taking, including: prescription drugs; over the counter drugs; heartworm, flea & tick medications; vitamins and supplements, including herbal medications.

Tell your veterinarian if your dog is pregnant, nursing puppies, or is intended for breeding purposes.

How do I give Palladia to my dog?
Palladia should be given to your dog by mouth (orally).

Palladia may be hidden inside a treat; be certain your dog swallows the entire tablet(s).

Follow your veterinarian’s instructions for how much and how often to give Palladia.
See the Handling Instructions section below in order to administer Palladia safely to
your dog.

How will Palladia affect my dog?
Palladia may help shrink your dog’s tumor. Like other cancer treatments, it can be
difficult to predict whether your dog’s tumor will respond to Palladia, and if it does
respond, how long it will remain responsive to Palladia. Regular check ups by your
veterinarian are necessary to determine whether your dog is responding as expected,
and to decide whether your dog should continue to receive Palladia.

What are some possible side effects of Palladia?
Like all drugs, Palladia may cause side effects, even at the prescribed dose. Serious
side effects can occur, with or without warning, and may in some situations result in death.
    • The most common side effects which may occur with Palladia include diarrhea,
    decreased or loss of appetite, lameness, weight loss and blood in the stool.

Stop Palladia immediately and contact your veterinarian if you notice any of the following changes in your dog:
   • Refusal to eat
   • Vomiting or watery stools (diarrhea), especially if more frequent than two times in 24 hours
   • Black tarry stools
   • Bright red blood in vomit or stools
   • Unexplained bruising or bleeding
   • Or if your dog experiences other changes that concern you

There are other side effects which may occur. For a more complete list, ask your veterinarian.


What do I need to know to handle Palladia safely?
Because Palladia is an anti-cancer drug, extra care must be taken when handling the
tablets, giving the drug to your dog and cleaning up after your dog.

Palladia is not for use in humans.

You should keep Palladia in a secure storage area out of the reach of children. Children should not come in contact with Palladia. Keep children away from feces, urine, or vomit of treated dogs.

If you are pregnant, a nursing mother, or planning to become pregnant and you choose to administer Palladia to your dog, you should be particularly careful and follow the handling procedures described below.

Palladia prevents the formation of new blood vessels in tumors. In a similar manner Palladia may affect blood vessel formation in the developing fetus and may harm an unborn baby (cause birth defects). For pregnant women, accidental ingestion of Palladia ay have adverse effects on pregnancy.

If Palladia is accidentally ingested by you or a family member, seek medical advice immediately. It is important to show the treating physician a copy of the package insert or label. In cases of accidental human ingestion of Palladia, you may experience gastrointestinal discomfort, including vomiting or diarrhea.

The following handling procedures will help to minimize exposure to the active ingredient in Palladia for you and other members of your household:

Anyone who administers Palladia to your dog should wash their hands after handling

When you or others are handling the tablets:
• Do not split or break the tablets to avoid disrupting the protective film coating.
• Palladia tablets should be administered to your dog immediately after they are removed from the bottle.
• Protective gloves should be worn if handling broken or moistened tablets. If your dog spits out the Palladia tablet, the tablet will be moistened and should be handled with protective gloves.
• If the Palladia tablet is “hidden” in food, make sure that your dog has eaten the entire dose. This will minimize the potential for exposure to children or other household members.

Cleaning up after your dog:
• Because Palladia is present in the stool, urine and vomit of dogs under treatment, you must wear protective gloves to clean up after your treated dog.
• While your dog receives Palladia, place the stool, feces or vomit, and any disposable towels used to clean up in a plastic bag which should be sealed for general household disposal. This will minimize the potential for exposure to people in contact with the trash.
• You should not wash any items soiled with stool, urine or vomit from your dog with other laundry.

This client information sheet gives the most important information about Palladia. For more information about Palladia, talk with your veterinarian.

To report a suspected adverse reaction call Pfizer Animal Health at 1-800-366-5288.

Made in Italy
Distributed by Pharmacia & Upjohn Company
Division of Pfizer Inc, New York, NY 10017
Issued March 31, 2009

Mast Cell Tumors in Dogs

Dr. Gail Mason, DVM, MA, DACVIM
Kathi L. Smith, RVT

Mast cell tumors (MCTs) are fairly common tumors in dogs. They are most frequently found in the superficial layers of the skin, on any part of the body. Frequently, there will be ulceration over the area of the tumor, and the dog may scratch or bite at the affected area. The appearance of the tumor does not reveal its potential for spread or recurrence with any certainty. The tumors are usually singular, but dogs may present with multiple nodules, or recurrent ones. Some nodules occasionally enlarge and then regress in size on their own, due to swelling within the tumor itself. This should always raise the suspicion of the presence of an MCT.

Diagnosis of Mast Cell Tumors

Mast cell tumors do not have a specific appearance. However, they are fairly easily detected by a "needle aspirate and cytology." Insertion of a small needle into the tumor (virtually painless) area is followed by examination of the cells under a microscope. Mast cells are large, round cells that usually have dark granules in them. The granules contain substances which, when released, cause swelling, itching, and redness. Infrequently, when a large number of granules spontaneously discharge their chemical contents into the bloodstream, vomiting, stomach ulcers, shock and even death may result.

Mast Cell Tumor Staging

Mast cell tumors can be somewhat unpredictable in their behavior, relative to other types of tumors in dogs. Because of this, care is taken to "grade" the tumors that are discovered. The grade reflects the degree to which the malignant mast cells differ from normal, non-malignant mast cells. The stage can generally be correlated with tumor behavior, tumor recurrence, and survival of the patient. Mast cell tumors affecting the limbs, head, or neck tend to correlate with a more favorable prognosis than those found on the trunk or groin. Multiple mast cell tumors or those exhibiting rapid growth tend to have a more guarded prognosis. A pathologist determines the tissue grade of the tumor after the tumor is biopsied or removed.

*Grade I: well-differentiated-25% recurrence rate post-surgery

*Grade II: moderately differentiated-44% recurrence rate post-surgery

*Grade III: poorly differentiated-76% recurrence rate post-surgery


Treatment for Mast Cell Tumors

Treatment for mast cell tumors may involve surgery (the mainstay), chemotherapy, and/or radiation therapy. Recommendations for treatment are based on the type and grade of the tumor, surgical feasibility, and the presence or absence of spread (dissemination) of malignant mast cells throughout the body. Your veterinarian will usually submit blood tests and request abdominal ultrasound or radiographs (x-rays) to determine the likelihood of malignant mast cells elsewhere in the dog's body. Bone marrow biopsies are no longer routinely done, as they have not shown to have high predictive value for tumor staging.


For single mast cell tumors, a surgical procedure known as a "wide resection" by an experienced surgeon is performed. This means aggressively excavating the tumor and surrounding tissues so that at least 2-3 cm of normal tissue in all directions is removed. This must include a "deep margin" which involves removing tissue below the tumor. The margins of the removed tissue are marked and examined by a pathologist to determine the presence of any lingering malignant cells. If negative, we refer to it as "clean margins". If the pathologist suspects the presence of mast cells in the remaining tissues of the surgery site, we refer to it as "dirty margins". If the remaining, malignant cells are less than 2 cm from the edge of the biopsy specimen, it is referred to as "close margins".

An aggressive surgery early in the course of mast cell tumor disease is associated with the best overall prognosis. A grade I or II tumor that has been completely removed usually requires no other immediate therapy. A grade III tumor, multiple tumors, recurrent tumors, or tumors with dirty margins (those which for anatomical reasons could not be subjected to further surgery) often require follow-up or "adjunct" therapy.

Radiation Therapy
Radiation therapy is an option for dogs whose mast cells tumors are localized, but too large for a clean resection or in an area difficult to resect such as tissues of the facial region, or as follow-up therapy for tumors with dirty margins. Dogs tolerate radiation therapy well, and it can offer long-term control for these tumors. Radiation therapy would not be appropriate for dogs with multiple tumors or those with evidence of disease throughout the body since the radiation beam treats only a single focus of disease. Radiation treatment can be accessed at New England Veterinary Oncology Group (NEVOG) in Waltham MA., Angell Memorial Animal Hospital in Boston, MA. and Tufts University School of Veterinary Medicine in Grafton, MA. This is a highly specialized form of therapy and we are pleased to refer your pet to these centers if need arises.

Chemotherapy denotes the administration of certain anti-cancer drugs in order to delay/prevent tumor growth or spread. It may be used before or after surgery, or alone.

Prednisone (a cortisone) is the most commonly used drug for therapy of mast cell tumors. It is well tolerated by dogs and is usually employed for a minimum of six months. If no new tumors appear within that time, your doctor may wean your dog off the prednisone completely. The side effects of prednisone include weight gain, increased appetite and thirst, bladder or skin infections, and panting. Occasionally, stomach irritation or ulcers can occur, or inflammation of the pancreas. Most of the time, the drug dose can be titrated to the patient to minimize any overt symptoms. If the tumor type is determined to be aggressive, additional drugs such as stomach protectants may be prescribed to guard against untoward tumor effects. By itself, prednisone is considered to have only mild anti-cancer effects on MCTS.

Chlorambucil Protocol
If your pet is deemed to have an increased risk of tumor recurrence, we may recommend combination oral therapy with prednisone and chlorambucil (Leukeran¨). Chlorambucil is a chemotherapy drug that is extremely well tolerated in most patients and yet offers more tumor protection than prednisone alone. This drug is usually administered twice weekly and requires that your pet be monitored at least every 6-8 weeks. The minimum treatment period is 6 months.

Vinblastine Protocol
For recurrent or multiple tumors, and for those tumors that cannot be surgically removed, combination chemotherapy can be effective in controlling tumor growth and spread for weeks to months or more. A cure per se is generally not realistic, but many dogs tolerate therapy extremely well. The six-month protocol involves:

Prednisone: high dose at first, then taper over 4 months
Vinblastine: an outpatient injection, given once every 21 days
Cyclophosphamide (Cytoxan¨): an oral chemotherapy drug, given by the owners on days 8,9,10, and 11 of a 21-day cycle.

This protocol has produced a 1 and 2 year survival rate for grade 2 tumors of 91%. For patients with grade 3 tumors, the 1-year survival rate is 66%.

Side Effects
The side effects of prednisone are discussed above. Vinblastine and Cytoxan have the ability to cause nausea and or vomiting, though this is not usual. The most important possible side effects are lowering the body's defenses so that infections occurs, or (rarely) causing many mast cells to release their contents at once. Both situations can be life threatening. However, these are NOT common, and the risk of these is significantly lower than the risk of untreated mast cell disease. You will be given instructions on what to do if any side effects occur, so do not hesitate to contact us.

Lomustine (CeeNu¨) 
CeeNu is a potent oral chemotherapy drug that can be used once every three weeks in patients who MCTs have become resistant to other treatments. It is very well tolerated in general. However, because it can increase the risk of infection (especially seven days after it is given), any noted fever, depression, weakness, or refusal to eat should be reported to us or your veterinarian, or an emergency hospital immediately. Infection is almost always completely reversible. This drug is more potent than Cytoxan¨ and maybe substituted for it if indicated. Occasionally, this drug may decrease patient blood cell counts, which requires a dose reduction or discontinuance.

The factors that are known to influence patient outcome are grade of tumor (I is best, III is most dangerous), completeness of surgical removal (clean margins), and tumor location. Dogs with high-grade tumors, multiple or recurrent tumors, or evidence of spread to the bloodstream or other organs have a much more guarded prognosis for a lengthy survival.

Patient Monitoring
Close patient monitoring is essential in dogs with a history of mast cell tumors. As with many tumors, early detection and treatment increases the chances of successful treatment. You may be asked to have your dog examined and monitored every 6-8 weeks following surgery, or every 21 days during chemotherapy. Blood tests and/or needle aspirates are often requested to assess tumor control. Any time you suspect a new or recurrent tumor, or that your dog is physically ill, contact us immediately. We welcome the opportunity to help you and your dog in any manner we can.


Reference: Mast cell tumors in dogs; In: Managing The Veterinary Cancer Patient; Ogilvie, OK and Moore, As. © 1995 Veterinary Learning Systems. Trenton, NJ. *Based on protocol published by Elmslie, Robin; published in the Veterinary Cancer Newsletter.