How Does Palladia (Toceranib) Work in Dogs?

Palladia is the brand name for toceranib phosphate, an oral cancer drug given at home, usually every other day. It was approved by the FDA in 2009 and was the first drug ever developed and approved specifically to treat cancer in dogs.

It works in two ways at once, which is what makes it different from conventional chemotherapy.

It switches off a growth signal inside tumor cells. Toceranib blocks enzymes called tyrosine kinases — in particular one called KIT. In roughly a third of canine mast cell tumors, a mutation leaves KIT permanently switched on, telling the cell to keep dividing. Toceranib blocks that signal.

It cuts off the tumor's blood supply. It also blocks receptors that tumors use to build new blood vessels. Without a growing blood supply, a tumor struggles to expand — and this second mechanism explains why the drug helps some dogs whose tumors have no KIT mutation at all.

Conventional chemotherapy attacks all rapidly dividing cells and is given by injection in a clinic. Toceranib interferes with specific signalling pathways and is given as a tablet at home. It is not a cure. Success means the tumor shrinks, stops growing, or grows more slowly — and stable disease genuinely counts as a good outcome.

Key points

• Palladia is FDA approved for recurrent grade 2 and 3 mast cell tumors in dogs, with or without lymph node involvement, and is the only oral targeted cancer drug approved for dogs in the US.
• It has two mechanisms — blocking the KIT growth signal, and blocking new blood vessel formation.
• In the pivotal trial, 37.2% of treated dogs responded during the blinded phase, versus 7.9% on placebo. Across all 145 dogs treated, the response rate was 42.8%, with about 60% getting some clinical benefit.
• Dogs whose tumors carry a KIT mutation are roughly twice as likely to respond — 69% versus 37%. Testing for this mutation is available.
• It is used off-label for many other cancers, including anal sac and thyroid carcinoma, where response rates around 25% are reported with stable disease in a further 50–60%.
• The label dose is widely considered higher than necessary. Many oncologists use lower doses to reduce side effects while keeping the drug working.
• Diarrhea and appetite loss are the most common side effects, and there are specific thresholds at which the drug should be paused.
• Monitoring is ongoing — bloodwork, weight, blood pressure, and urine protein.

Detailed explanation

What a tyrosine kinase inhibitor actually does

Cells contain proteins called tyrosine kinases that act as switches in signalling chains. When a growth signal arrives, the switch flips on and the cell divides. Normally the signal stops and the switch flips off.

In many cancers, a mutation leaves the switch jammed on. The cell receives a constant instruction to divide, with no external signal required. A tyrosine kinase inhibitor is a drug that binds to that switch and prevents it from firing.

This is a different approach from conventional chemotherapy, which kills cells that happen to be dividing quickly — cancer cells, but also bone marrow and gut lining cells, which is where its side effects come from. A targeted drug interferes with a specific pathway instead. That does not make it free of side effects, since normal cells use these pathways too, but the side-effect profile is different.

Mechanism one: blocking KIT

Mast cells naturally carry a receptor called KIT that regulates their growth and survival. In roughly one third of canine mast cell tumors, the c-KIT gene is mutated in a way that leaves the receptor permanently active — driving continuous, unregulated division.

Toceranib blocks KIT. In tumors where that jammed switch is the engine driving the cancer, removing it can produce a striking effect.

This is why KIT mutation status predicts response so well. In the pivotal trial, dogs whose tumors carried an activating KIT mutation responded at roughly twice the rate of dogs whose tumors did not — 69% compared with 37%.

This is worth asking about. Testing for c-KIT mutations is available and is standard practice for higher-grade mast cell tumors. It identifies the dogs most likely to benefit, which is useful information before committing to a treatment that requires ongoing monitoring and cost.

A nuance worth knowing: mast cell tumors with KIT mutations tend to be more biologically aggressive to begin with. So a mutation predicts a better chance of responding to this specific drug, while also indicating a tumor that would otherwise behave less favourably.

Mechanism two: cutting off the blood supply

Toceranib also blocks receptors called VEGFR2 and PDGFR, which tumors use to recruit new blood vessels.

Solid tumors cannot grow beyond a small size without building their own blood supply. Blocking that process — antiangiogenesis — starves the tumor of what it needs to expand.

This second mechanism is why toceranib has activity in cancers that have nothing to do with mast cells or KIT. It is the basis for its widespread off-label use, and for the fact that some dogs without KIT mutations still respond.

What "working" looks like

Owner expectations often centre on the tumor disappearing. With this drug, several outcomes count as success:

• Complete response — the tumor is no longer detectable
• Partial response — the tumor shrinks meaningfully
• Stable disease — the tumor stops growing

That last category matters. A tumor held stable for months, in a dog feeling well, is a real result. Trials report it separately as "clinical benefit" precisely because stopping progression has value even without shrinkage.

In the pivotal study, the response rate during the blinded phase was 37.2% for treated dogs versus 7.9% on placebo. Across all 145 dogs who eventually received the drug, 42.8% had an objective response, and adding those with stable disease brought overall clinical benefit to around 60%. Median duration of response was about 18 weeks. Dogs without lymph node metastasis responded better than those with it — 67% versus 46%.

Off-label uses

Toceranib is approved only for mast cell tumors, but it is used off-label for many others — a normal and accepted practice in veterinary oncology, where few drugs carry species-specific approvals.

Reported activity includes anal sac (apocrine gland) adenocarcinoma and thyroid carcinoma, where objective response rates around 25% have been reported with stable disease in a further 50–60% of dogs. It has also been used for head and neck carcinoma, nasal carcinoma, metastatic osteosarcoma, various sarcomas, melanoma, and heart-base tumors.

Off-label does not mean experimental or unsupported. It means the studies exist but a formal approval for that use does not.

How it is given, and the dosing question

Toceranib is a tablet given at home, typically every other day, with or without food.

Here is a point worth raising with your veterinarian: the label dose is considered by most clinicians to be higher than necessary, and is associated with more side effects. Studies of lower doses have found reduced adverse effects while maintaining drug levels sufficient for biological activity. Many oncologists now start lower than the label dose as standard.

If your dog is struggling with side effects, this is a legitimate conversation — dose reduction is a normal part of managing this drug, not an admission that treatment has failed.

Handling matters. Toceranib is classed as a hazardous drug. Wear gloves when handling the tablets, never split or crush them, do not handle them in food preparation areas, and wear gloves when cleaning up your dog's waste. Anyone pregnant, breastfeeding, trying to conceive, or immunocompromised should not handle the drug or the treated dog's waste.

Side effects and monitoring

Gastrointestinal effects are the most common: diarrhea, reduced or absent appetite, weight loss, vomiting, and blood in the stool. Less commonly, dogs develop high blood pressure, protein loss in the urine, changes in blood cell counts, liver enzyme elevations, lameness or muscle soreness, and rarely pancreatitis.

Serious gastrointestinal complications including ulceration and perforation have occurred, though rarely. The drug is known to be ulcerogenic, which is why anti-inflammatories must be used with caution alongside it — the combination raises the risk of ulceration or perforation. If another practice prescribes an NSAID for something unrelated, make sure they know your dog is on Palladia.

Monitoring is ongoing and includes bloodwork, body weight, blood pressure, and urinalysis to check for protein loss. Typically this is weekly for the first several weeks, then less often once a dog is stable.

Know the thresholds for pausing the drug. Veterinary guidance advises temporarily stopping toceranib if a dog has more than two episodes of vomiting or diarrhea in 24 hours, loses its appetite, has fresh blood in the stool for more than two days, or develops unexplained bruising. Report any of these; a dose reduction usually follows once your dog is back to normal.

Ask for these written down when the drug is first dispensed. They are exactly what you cannot recall on a Sunday evening.

Drug holidays are normal. Pausing for a few days to let side effects settle, then restarting at a lower dose, is standard management rather than a sign the treatment is failing.

Resistance

Dogs that respond to toceranib generally do eventually progress. Tumors develop resistance over time, which is an active area of research.

This is worth knowing in advance so that progression is understood as part of the expected course rather than something that went wrong. When it happens, other options may still exist, and it is a reasonable point to ask about referral or reassessment.

When to contact a veterinarian

Stop the medication and contact your veterinarian if your dog:

• Has more than two episodes of vomiting or diarrhea in 24 hours
• Stops eating
• Has fresh blood in the stool for more than two days
• Develops unexplained bruising

Seek emergency care immediately if your dog:

• Is vomiting blood, or passing black tarry stool
• Has severe abdominal pain, or a tense painful abdomen
• Is collapsed, very weak, or has pale gums
• Cannot keep water down
• Has facial swelling, hives, or difficulty breathing

Contact your veterinarian within a day if your dog:

• Has ongoing mild diarrhea or a reduced appetite
• Is losing weight
• Has become lame, stiff, or sore
• Seems unusually tired or flat
• Is due for monitoring bloodwork, blood pressure, or urinalysis

Always tell any veterinarian treating your dog — including emergency clinics and other practices — that your dog is on Palladia, particularly before an anti-inflammatory is prescribed.

Questions to ask your veterinarian

• Has my dog's tumor been tested for a c-KIT mutation, and would that change what we expect?
• What are we hoping for — shrinkage, or holding the tumor stable?
• What starting dose are you using, and is it lower than the label dose?
• What monitoring will my dog need, and how often?
• At exactly what point should I stop giving it and call you? Can you write that down?
• What side effects should I expect early on, and which would worry you?
• Can I have anti-nausea and anti-diarrheal medications to keep at home?
• Is my dog on any medication that interacts with this, particularly an anti-inflammatory?
• What handling precautions do I need at home?
• How will we know whether it is working, and when will we reassess?
• If it stops working, what are the next options?

Sources

American Animal Hospital Association. (2026). 2026 AAHA oncology guidelines for dogs and cats: Therapeutic modalities — chemotherapy. https://www.aaha.org/resources/2026-aaha-oncology-guidelines-for-dogs-and-cats/section-5-therapeutic-interventions/therapeutic-modalities-chemotherapy/

Christensen, J., Johnson, K., Ettinger, S., Garrett, L., Gordon, I., Ireifej, S., Love, A., & Wisecup, M. (2026). AAHA oncology guidelines for dogs and cats. Journal of the American Animal Hospital Association, 62(1), 1–37. https://doi.org/10.5326/JAAHA-MS-7549

Halsey, C. H. C., Rose, B. J., Gustafson, D. L., & Thamm, D. H. (2012). Canine mast cell tumor and toceranib phosphate (Palladia): Development of a spontaneous canine model of kinase inhibitor resistance. Clinical Cancer Research, 18(10 Suppl), A56.

London, C. A., Malpas, P. B., Wood-Follis, S. L., et al. (2009). Multi-center, placebo-controlled, double-blind, randomized study of oral toceranib phosphate (SU11654), a receptor tyrosine kinase inhibitor, for the treatment of dogs with recurrent (either local or distant) mast cell tumor following surgical excision. Clinical Cancer Research, 15(11), 3856–3865. https://doi.org/10.1158/1078-0432.CCR-08-1860

BMC Veterinary Research. (2013). Evaluation of expression and function of vascular endothelial growth factor receptor 2, platelet derived growth factor receptors-alpha and -beta, KIT, and RET in canine apocrine gland anal sac adenocarcinoma and thyroid carcinoma. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3542001/

BMC Veterinary Research. (2013). Evaluation of the adverse event profile and pharmacodynamics of toceranib phosphate administered to dogs with solid tumors at doses below the maximum tolerated dose. https://pmc.ncbi.nlm.nih.gov/articles/PMC3850926/

Michigan State University Veterinary Diagnostic Laboratory. (n.d.). Canine mast cell tumors: A guide for pet owners. https://cvm.msu.edu/vdl/client-education/guides-for-pet-owners/canine-mast-cell-tumors

VCA Animal Hospitals. (n.d.). Toceranib phosphate. https://vcahospitals.com/know-your-pet/toceranib-phosphate

Veterinary Information Network. (n.d.). Toceranib phosphate (Palladia). Veterinary Partner. https://veterinarypartner.vin.com/default.aspx?pid=19239&catId=102894&id=4952879

Zoetis. (n.d.). Palladia (toceranib phosphate) tablets — client information sheet. DailyMed, U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/medguide.cfm?setid=ae09ae83-0812-4ddc-92e3-730f7a1ae449

This article is for educational purposes only and is not a substitute for veterinary care. It describes how this medication works in general terms and deliberately does not include doses. Palladia is a prescription medication that should only be given under veterinary direction, and dose changes should never be made without consulting your veterinarian. If your dog is vomiting blood, passing black tarry stool, is collapsed or very weak, or is having difficulty breathing, seek emergency veterinary care immediately.